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1
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Lebedev E, Smutin D, Timkin P, Kotelnikov D, Taldaev A, Panushev N, Adonin L. The eusocial non-code: Unveiling the impact of noncoding RNAs on Hymenoptera eusocial evolution. Noncoding RNA Res 2025; 11:48-59. [PMID: 39736856 PMCID: PMC11683303 DOI: 10.1016/j.ncrna.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 10/14/2024] [Accepted: 10/27/2024] [Indexed: 01/01/2025] Open
Abstract
Eusociality, characterized by reproductive division of labor, cooperative brood care, and multi-generational cohabitation, represents a pinnacle of complex social evolution, most notably manifested within the Hymenoptera order including bees, ants, and wasps. The molecular underpinnings underlying these sophisticated social structures remain an enigma, with noncoding RNAs (ncRNAs) emerging as crucial regulatory players. This article delves into the roles of ncRNAs in exerting epigenetic control during the development and maintenance of Hymenopteran eusociality. We consolidate current findings on various classes of ncRNAs, underscoring their influence on gene expression regulation pertinent to caste differentiation, developmental plasticity, and behavioral modulation. Evidence is explored supporting the hypothesis that ncRNAs contribute to epigenetic landscapes fostering eusocial traits through genomic regulation. They are likely to play an important role in eusociality "point of no return". Critical analysis is provided on the functional insights garnered from ncRNA profiles correlated with caste-specific phenotypes, specifical for phylogenetic branches and transitional sociality models, drawing from comparative genomics and transcriptomics studies. Overall, ncRNA provides a missed understanding of both "genetic toolkit" and "unique genes" hypotheses of eusociality development. Moreover, it points to gaps in current knowledge, advocating for integrative approaches combining genomics, proteomics, and epigenetics to decipher the complexity of eusociality. Understanding the ncRNA contributions offers not only a window into the molecular intricacies of Hymenoptera sociality but also extends our comprehension of how complex biological systems evolve and function.
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Affiliation(s)
- Egor Lebedev
- Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, 625003, Tyumen, Russia
| | - Daniil Smutin
- Faculty of Information Technology and Programming, ITMO University, St.-Petersburg, 197101, Russia
| | - Pavel Timkin
- All-russian Research Institute of Soybean, 675027, Blagoveschensk, Russia
| | - Danil Kotelnikov
- All-russian Research Institute of Soybean, 675027, Blagoveschensk, Russia
- Institute of Biomedical Chemistry, Moscow, 119121, Russia
| | - Amir Taldaev
- Institute of Biomedical Chemistry, Moscow, 119121, Russia
- Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia
| | - Nick Panushev
- Bioinformatics Institute, 197342, St.-Petersburg, Russia
| | - Leonid Adonin
- Institute of Environmental and Agricultural Biology (X-BIO), Tyumen State University, 625003, Tyumen, Russia
- Institute of Biomedical Chemistry, Moscow, 119121, Russia
- Federal State Budget-Financed Educational Institution of Higher Education The Bonch-Bruevich Saint Petersburg State University of Telecommunications, Saint-Petersburg, 193232, Russia
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2
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Luan H. Cell-Autonomous and Non-Cell-Autonomous Antiviral Immunity via siRNA-Directed RNAi in Drosophila melanogaster. IMMUNE DISCOVERY 2025; 1:10001. [PMID: 39926592 PMCID: PMC11800332 DOI: 10.70322/immune.2025.10001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
Abstract
In Drosophila melanogaster, the siRNA-directed RNAi pathway provides crucial antiviral defenses. Cell-autonomously, Dicer-2 (Dcr-2) recognizes and cleaves viral dsRNA into siRNAs, which are incorporated into the RNA-induced silencing complex (RISC). Argonaute 2 (Ago2) then targets and cleaves viral RNA, preventing replication. Non-cell-autonomously, infected hemocytes secrete exosomes containing viral siRNAs, spreading antiviral signals to other cells. Additionally, tunneling nanotubes can transfer RNAi components between neighboring cells, further enhancing systemic immunity. These findings highlight the sophisticated antiviral strategies in Drosophila, offering insights for broader antiviral research.
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Affiliation(s)
- Haojiang Luan
- Section on Neural Function, LMB, NIMH, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA
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3
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Li W, Liu WJ, Lu J, Ma F, Zhang CY. A Programmable Automatic Cascade Machinery for Single-Molecule Profiling of Multiple Noncoding RNAs in Breast Tissues. Anal Chem 2025; 97:4224-4232. [PMID: 39930751 DOI: 10.1021/acs.analchem.4c07017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
Noncoding RNAs (ncRNAs) are identified as critical regulatory molecules in tumorigenesis and progression. Investigating the expression patterns of multiple ncRNAs in living cells and tissues may facilitate the diagnosis of cancers. Herein, we develop a programmable automatic cascade machinery for single-molecule profiling of multiple ncRNAs. This method involves two successive amplification events that can convert extremely low-abundance target ncRNAs into abundant FAM/Cy5 molecules for the generation of amplified fluorescence signals. The subsequent single-molecule detection can identify piR-36026 with the FAM signal and DSCAM-AS1 with the Cy5 signal. Due to the high efficiency of automatic cascade machinery and the high signal-to-noise ratio of single-molecule imaging, this method can achieve sensitive detection of multiple ncRNAs with a detection limit of 44.67 aM for piR-36026 and 45.71 aM for DSCAM-AS1, and it can measure endogenous piR-36026 and DSCAM-AS1 at the single-cell level. Moreover, the profiling of piR-36026 and DSCAM-AS1 in healthy tissues and breast cancer tissues demonstrates the feasibility of the proposed method in cancer diagnostics. By programming the recognition sequences of dumbbell probes, this method can be extended to measure other cancer-related ncRNAs, with great prospects in clinical applications.
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Affiliation(s)
- Wen Li
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Wen-Jing Liu
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Jun Lu
- Auckland Bioengineering Institute, University of Auckland, Auckland 1142, New Zealand
| | - Fei Ma
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Chun-Yang Zhang
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
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4
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Cai J, Yan Z, Zhong Y, Li Y, Huang J, Hu H, Li Y, Fang H, Wu S. Small non-coding RNA profiling in patients with non-muscle invasive bladder cancer. BMC Cancer 2025; 25:319. [PMID: 39984879 PMCID: PMC11846270 DOI: 10.1186/s12885-025-13672-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 02/06/2025] [Indexed: 02/23/2025] Open
Abstract
The intricate regulatory roles of small non-coding RNAs (sncRNAs), including PIWI-interacting RNAs (piRNAs) and microRNAs (miRNAs), have been increasingly recognized in the modulation of cellular functions and are associated with the pathogenesis of various diseases, notably cancer. However, the specific dysregulation patterns of sncRNAs in non-muscle-invasive bladder cancer (NMIBC) have yet to be fully delineated, highlighting a significant gap in our current understanding. To elucidate the expressional dynamics of sncRNAs for patients with NMIBC, we characterized the profile of piRNAs and miRNAs by next-generation sequencing. We identified the differentially expressed sncRNAs between tumor and paracancerous tissues and characterized their distribution along the genome. We further revealed a set of immune-related piRNAs and dysregulated miRNAs that might be associated with NMIBC pathogenesis. Differentially expressed piRNAs were predominantly localized at the long arms of chromosomes 13, 1, and 6. Notably, the targets of specific piRNAs, including piR-hsa-2215234, piR-hsa-105306, piR-hsa-102066, and piR-hsa-236465, show significant associated with antigen processing and presentation pathway. Additionally, differentially expressed miRNAs are mainly located on chromosome 14 and their target genes tend to be involved in cancer-related pathways, suggesting their potential regulatory roles in NMIBC. Collectively, this study revealed the global sncRNA dysregulation in NMIBC, and the identified sncRNAs are implicated in the modulation of both immune and cancer pathways, suggesting their contribution to the pathogenesis and potential targets for immunotherapy.
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Affiliation(s)
- Jiajia Cai
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
| | - Zeqin Yan
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
| | - Yadi Zhong
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
- Department of Urology, The Affiliated Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen, 518009, China
| | - Yuqing Li
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
| | - Jianxu Huang
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
| | - Huijuan Hu
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
| | - Yingrui Li
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China
- Department of Urology, Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, China
| | - Hu Fang
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China.
- Institute of Biomedical Data, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China.
| | - Song Wu
- Department of Experimental Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518000, China.
- Department of Urology, Third Affiliated Hospital of Shenzhen University, Shenzhen, 518000, China.
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5
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Yang DM, Li D, Zhang Q, Zhao S, Zhang CY. Development of a Single-Molecule Biosensor Based on Polymerization-Transcription-Mediated Target Regeneration for Simultaneously One-Pot Detection of Multiple piRNAs. Anal Chem 2025; 97:3145-3152. [PMID: 39882705 DOI: 10.1021/acs.analchem.4c06491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
PIWI-interacting RNAs (piRNAs) are a class of small noncoding RNAs associated with PIWI proteins within the male germline, and they play significant roles in maintaining genome stability via the modulation of gene expression. The piRNAs are implicated in the progression of various cancers, but the simultaneous monitoring of multiple piRNAs remains a challenge. Herein, we construct a single-molecule biosensor based on polymerization-transcription-mediated target regeneration for the simultaneous one-pot detection of multiple piRNAs. This assay involves two cycles. In step 1, target piRNAs hybridize with the template probe complexes to yield three-way junction (3WJ) structures. Then, KF DNA polymerase initiates the extension to generate a complete T7 promoter, and the extension product can act as an invading strand to displace signal probes, resulting in the release of fluorophores. Then, in step 2, the T7 promoter can be recognized by T7 RNA polymerase to initiate transcription, producing abundant transcripts with 3'-OH that are identical to piRNAs. The resultant transcripts can hybridize with free template probe complexes to obtain new 3WJ structures that can be elongated by KF polymerase for the recovery of fluorescence signals. This assay can be performed homogeneously in a one-pot format within 30 min, and it exhibits high sensitivity, with a limit of detection (LOD) of 19.26 aM for piRNA-36026 and 41.88 aM for piRNA-36743. Moreover, it can simultaneously detect endogenous piRNAs at the single-cell level and differentiate piRNA expression in the tissues of healthy individuals and breast cancer patients, offering a prospective platform for clinic diagnosis.
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Affiliation(s)
- Dong-Ming Yang
- State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of Education, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China
| | - Dongling Li
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Qian Zhang
- School of Chemistry and Materials Science, Ludong University, Yantai 264025, China
| | - Shulin Zhao
- State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of Education, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China
| | - Chun-Yang Zhang
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
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6
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Karami Y, Ehtiati S, Ghasemi H, Rafiee M, Zamani Sani M, Hosseini SE, Moradi Kazerouni H, Movahedpour A, Aiiashi S, Khatami SH. Non-coding RNA biosensors for early detection of brain cancer. Clin Chim Acta 2025; 566:120041. [PMID: 39561887 DOI: 10.1016/j.cca.2024.120041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/11/2024] [Accepted: 11/11/2024] [Indexed: 11/21/2024]
Abstract
Brain cancer remains a formidable challenge with limited treatment options. Non-coding RNAs (ncRNAs) have emerged as promising biomarkers due to their dysregulation in tumorigenesis. This review explores the potential of biosensors for early detection of brain cancer by targeting ncRNAs. We discuss the classification and functions of ncRNAs, emphasizing their involvement in key cancer-related processes. Additionally, we delve into recent advancements in biosensor technology, focusing on their ability to accurately detect specific ncRNA biomarkers associated with brain cancer. Our findings underscore the potential of biosensors to revolutionize brain cancer diagnosis, enabling personalized medicine and improving patient outcomes. Future research should focus on refining biosensor technology and expanding their clinical application.
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Affiliation(s)
- Yousof Karami
- Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Sajad Ehtiati
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran
| | - Maedeh Rafiee
- Department of Veterinary Sciences University of Wyoming 1174 Snowy Range Road Laramie, WY 82070, USA
| | - Maryam Zamani Sani
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Edris Hosseini
- Resident of Large Animal Internal Medicine, Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Iran
| | | | - Ahmad Movahedpour
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Saleh Aiiashi
- Abadan University of Medical Sciences, Abadan, Iran.
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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7
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Silvia BJ, Shetty S, Behera R, Khandelwal A, Gore M, Bairy M, Ajjanagadde A, Shaheeda A, Bhat GK, Kabekkodu SP. A comprehensive review on the role of PIWI-interacting RNA (piRNA) in gynecological cancers. Life Sci 2024; 357:123065. [PMID: 39299387 DOI: 10.1016/j.lfs.2024.123065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 05/15/2024] [Accepted: 09/16/2024] [Indexed: 09/22/2024]
Abstract
Gynecological cancers are currently a major public health concern due to increase in incidence and mortality globally. PIWI-interacting RNA (piRNA) are small non-coding RNA consisting of 24-32 nucleotides that plays regulatory role by interacting with piwi family of protein. Recent studies have revealed that piRNAs are expressed in various kinds of human tissues and influences key signalling pathways at transcriptional and post transcriptional levels. Studies have also that suggested piRNA and PIWI proteins display frequently altered expression in several cancers. Recent research has indicated that abnormal expression of piRNA may play a significant role in development and progression of gynecological cancers. Clinical studies suggested that, abnormally expressed piRNAs may serve as diagnostic and prognostic marker, and as potential therapeutic targets in these cancers. In the present review article, we discussed the emerging role of piRNA and their utility as diagnostic and prognostic marker in gynecological cancers.
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Affiliation(s)
- Bobby J Silvia
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Sachin Shetty
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Roopal Behera
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Ayush Khandelwal
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Mrudula Gore
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Medha Bairy
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Anagha Ajjanagadde
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Aishath Shaheeda
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Gahan Krishna Bhat
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576106, India.
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8
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Jusic A, Erpapazoglou Z, Dalgaard LT, Lakkisto P, de Gonzalo-Calvo D, Benczik B, Ágg B, Ferdinandy P, Fiedorowicz K, Schroen B, Lazou A, Devaux Y, on behalf of EU-CardioRNA COST Action CA17129, AtheroNET COST Action CA21153. Guidelines for mitochondrial RNA analysis. MOLECULAR THERAPY. NUCLEIC ACIDS 2024; 35:102262. [PMID: 39091381 PMCID: PMC11292373 DOI: 10.1016/j.omtn.2024.102262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Mitochondria are the energy-producing organelles of mammalian cells with critical involvement in metabolism and signaling. Studying their regulation in pathological conditions may lead to the discovery of novel drugs to treat, for instance, cardiovascular or neurological diseases, which affect high-energy-consuming cells such as cardiomyocytes, hepatocytes, or neurons. Mitochondria possess both protein-coding and noncoding RNAs, such as microRNAs, long noncoding RNAs, circular RNAs, and piwi-interacting RNAs, encoded by the mitochondria or the nuclear genome. Mitochondrial RNAs are involved in anterograde-retrograde communication between the nucleus and mitochondria and play an important role in physiological and pathological conditions. Despite accumulating evidence on the presence and biogenesis of mitochondrial RNAs, their study continues to pose significant challenges. Currently, there are no standardized protocols and guidelines to conduct deep functional characterization and expression profiling of mitochondrial RNAs. To overcome major obstacles in this emerging field, the EU-CardioRNA and AtheroNET COST Action networks summarize currently available techniques and emphasize critical points that may constitute sources of variability and explain discrepancies between published results. Standardized methods and adherence to guidelines to quantify and study mitochondrial RNAs in normal and disease states will improve research outputs, their reproducibility, and translation potential to clinical application.
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Affiliation(s)
- Amela Jusic
- HAYA Therapeutics SA, Route De La Corniche 6, SuperLab Suisse - Batiment Serine, 1066 Epalinges, Switzerland
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445 Strassen, Luxembourg
| | - Zoi Erpapazoglou
- Ιnstitute for Fundamental Biomedical Research, B.S.R.C. “Alexander Fleming”, Vari, 16672 Athens, Greece
| | - Louise Torp Dalgaard
- Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark
| | - Päivi Lakkisto
- Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
- Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
| | - David de Gonzalo-Calvo
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, 25198 Lleida, Spain
- CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Bettina Benczik
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Center for Pharmacology and Drug Research & Development, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary
- Pharmahungary Group, 6722 Szeged, Hungary
| | - Bence Ágg
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Center for Pharmacology and Drug Research & Development, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary
- Pharmahungary Group, 6722 Szeged, Hungary
| | - Péter Ferdinandy
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Center for Pharmacology and Drug Research & Development, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary
- Pharmahungary Group, 6722 Szeged, Hungary
| | | | - Blanche Schroen
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, ER 6229 Maastricht, the Netherlands
| | - Antigone Lazou
- School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Yvan Devaux
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445 Strassen, Luxembourg
| | - on behalf of EU-CardioRNA COST Action CA17129
- HAYA Therapeutics SA, Route De La Corniche 6, SuperLab Suisse - Batiment Serine, 1066 Epalinges, Switzerland
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445 Strassen, Luxembourg
- Ιnstitute for Fundamental Biomedical Research, B.S.R.C. “Alexander Fleming”, Vari, 16672 Athens, Greece
- Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark
- Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
- Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, 25198 Lleida, Spain
- CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, 28029 Madrid, Spain
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Center for Pharmacology and Drug Research & Development, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary
- Pharmahungary Group, 6722 Szeged, Hungary
- NanoBioMedical Centre, Adam Mickiewicz University in Poznan, 61614 Poznan, Poland
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, ER 6229 Maastricht, the Netherlands
- School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - AtheroNET COST Action CA21153
- HAYA Therapeutics SA, Route De La Corniche 6, SuperLab Suisse - Batiment Serine, 1066 Epalinges, Switzerland
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445 Strassen, Luxembourg
- Ιnstitute for Fundamental Biomedical Research, B.S.R.C. “Alexander Fleming”, Vari, 16672 Athens, Greece
- Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark
- Minerva Foundation Institute for Medical Research, 00290 Helsinki, Finland
- Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, 25198 Lleida, Spain
- CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, 28029 Madrid, Spain
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Center for Pharmacology and Drug Research & Development, Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary
- Pharmahungary Group, 6722 Szeged, Hungary
- NanoBioMedical Centre, Adam Mickiewicz University in Poznan, 61614 Poznan, Poland
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, ER 6229 Maastricht, the Netherlands
- School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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9
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Tong W, Han Y, Wang T, Wan J, Ma F, Zhang CY. Bidirectional Polymerization-Transcription Amplification-Encoded Dual-Color Fluorescent Biosensor for Label-Free and Primer-Free Detection of Multiple piRNAs. Anal Chem 2024. [PMID: 39250656 DOI: 10.1021/acs.analchem.4c03773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Abstract
PIWI-interacting RNAs (piRNAs) are a type of endogenous noncoding RNAs with a length of 24-31 nucleotides, and they can specifically bind with PIWI proteins to form the piRNA/PIWI complexes for regulating multiple physiological and pathological processes. Herein, we develop a bidirectional polymerization-transcription amplification-encoded dual-color fluorescent biosensor for label-free and primer-free measurements of multiple piRNAs. The designed hairpin probe contains a palindromic tail, and it can serve as the target recognition unit, polymerization primer, and transcription template. In the presence of target piRNAs, the hairpin probes are opened to expose a palindromic sequence that can trigger bidirectional polymerization and transcription reaction with the assistance of KF polymerase and T7 RNA polymerase for the production of numerous RNA aptamers. The aptamers subsequently bind with the corresponding fluorophores (DFHBI-1T/MG) to form the RNA aptamer-fluorophore complexes for the generation of enhanced fluorescence signals. This biosensor can sensitively detect piR-36026 with a limit of detection (LOD) of 82.08 aM and piR-36743 with a LOD of 44.44 aM. Moreover, it can quantify cellular piRNAs with single-cell sensitivity and distinguish cancer cells from normal cells. Furthermore, it has the capability of distinguishing the expression of piRNAs in the tissues of breast cancer patients and healthy individuals. By simply altering the target recognition site of the hairpin probe, this biosensor can be extended to detect various piRNAs, offering a powerful platform for piRNA-related clinical diagnostics and therapeutics.
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Affiliation(s)
- Weijie Tong
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Yun Han
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Tao Wang
- Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210000, China
| | - Jiayi Wan
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Fei Ma
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Chun-Yang Zhang
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
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10
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Wang L, Xiao J, Zhang B, Hou A. Epigenetic modifications in the development of bronchopulmonary dysplasia: a review. Pediatr Res 2024; 96:632-642. [PMID: 38570557 DOI: 10.1038/s41390-024-03167-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 02/25/2024] [Accepted: 03/07/2024] [Indexed: 04/05/2024]
Abstract
While perinatal medicine advancements have bolstered survival outcomes for premature infants, bronchopulmonary dysplasia (BPD) continues to threaten their long-term health. Gene-environment interactions, mediated by epigenetic modifications such as DNA methylation, histone modification, and non-coding RNA regulation, take center stage in BPD pathogenesis. Recent discoveries link methylation variations across biological pathways with BPD. Also, the potential reversibility of histone modifications fuels new treatment avenues. The review also highlights the promise of utilizing mesenchymal stem cells and their exosomes as BPD therapies, given their ability to modulate non-coding RNA, opening novel research and intervention possibilities. IMPACT: The complexity and universality of epigenetic modifications in the occurrence and development of bronchopulmonary dysplasia were thoroughly discussed. Both molecular and cellular mechanisms contribute to the diverse nature of epigenetic changes, suggesting the need for deeper biochemical techniques to explore these molecular alterations. The utilization of innovative cell-specific drug delivery methods like exosomes and extracellular vesicles holds promise in achieving precise epigenetic regulation.
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Affiliation(s)
- Lichuan Wang
- Department of Pediatrics, Sheng Jing Hospital of China Medical University, Shenyang, China
| | - Jun Xiao
- Department of Pediatrics, Sheng Jing Hospital of China Medical University, Shenyang, China
| | - Bohan Zhang
- Department of Pediatrics, Sheng Jing Hospital of China Medical University, Shenyang, China
| | - Ana Hou
- Department of Pediatrics, Sheng Jing Hospital of China Medical University, Shenyang, China.
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11
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Yuan H, Hu J, Ge QQ, Liu WJ, Ma F, Zhang CY. Construction of a Spatial-Confined Self-Stacking Catalytic Circuit for Rapid and Sensitive Imaging of Piwi-Interacting RNA in Living Cells. NANO LETTERS 2024; 24:8732-8740. [PMID: 38958407 DOI: 10.1021/acs.nanolett.4c02230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
Abstract
Piwi-interacting RNAs (piRNAs) are small noncoding RNAs that repress transposable elements to maintain genome integrity. The canonical catalytic hairpin assembly (CHA) circuit relies on random collisions of free-diffused reactant probes, which substantially slow down reaction efficiency and kinetics. Herein, we demonstrate the construction of a spatial-confined self-stacking catalytic circuit for rapid and sensitive imaging of piRNA in living cells based on intramolecular and intermolecular hybridization-accelerated CHA. We rationally design a 3WJ probe that not only accelerates the reaction kinetics by increasing the local concentration of reactant probes but also eliminates background signal leakage caused by cross-entanglement of preassembled probes. This strategy achieves high sensitivity and good specificity with shortened assay time. It can quantify intracellular piRNA expression at a single-cell level, discriminate piRNA expression in tissues of breast cancer patients and healthy persons, and in situ image piRNA in living cells, offering a new approach for early diagnosis and postoperative monitoring.
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Affiliation(s)
- Huimin Yuan
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Jinping Hu
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Qi-Qin Ge
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Wen-Jing Liu
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Fei Ma
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
| | - Chun-Yang Zhang
- School of Chemistry and Chemical Engineering, State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 211189, China
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12
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Leng X, Zhang M, Xu Y, Wang J, Ding N, Yu Y, Sun S, Dai W, Xue X, Li N, Yang Y, Shi Z. Non-coding RNAs as therapeutic targets in cancer and its clinical application. J Pharm Anal 2024; 14:100947. [PMID: 39149142 PMCID: PMC11325817 DOI: 10.1016/j.jpha.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 01/12/2024] [Accepted: 02/01/2024] [Indexed: 08/17/2024] Open
Abstract
Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression. Oncogenes promote cell growth and proliferation, whereas tumor suppressor genes inhibit cell growth and division. The dysregulation of these genes can lead to the development of cancer. Recent studies have focused on non-coding RNAs (ncRNAs), including circular RNA (circRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), as therapeutic targets for cancer. In this article, we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets. Here, we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment. Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.
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Affiliation(s)
- Xuejiao Leng
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Mengyuan Zhang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yujing Xu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jingjing Wang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ning Ding
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yancheng Yu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Shanliang Sun
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Weichen Dai
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Xin Xue
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Nianguang Li
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Ye Yang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Zhihao Shi
- Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, 211198, China
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13
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Wu J, Niu L, Yang K, Xu J, Zhang D, Ling J, Xia P, Wu Y, Liu X, Liu J, Zhang J, Yu P. The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis. Ageing Res Rev 2024; 96:102234. [PMID: 38367813 DOI: 10.1016/j.arr.2024.102234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 02/06/2024] [Accepted: 02/13/2024] [Indexed: 02/19/2024]
Abstract
Osteoporosis is a prevalent chronic metabolic bone disease that poses a significant risk of fractures or mortality in elderly individuals. Its pathophysiological basis is often attributed to postmenopausal estrogen deficiency and natural aging, making the progression of primary osteoporosis among elderly people, especially older women, seemingly inevitable. The treatment and prevention of osteoporosis progression have been extensively discussed. Recently, as researchers delve deeper into the molecular biological mechanisms of bone remodeling, they have come to realize the crucial role of posttranscriptional gene control in bone metabolism homeostasis. RNA-binding proteins, as essential actors in posttranscriptional activities, may exert influence on osteoporosis progression by regulating the RNA life cycle. This review compiles recent findings on the involvement of RNA-binding proteins in abnormal bone metabolism in osteoporosis and describes the impact of some key RNA-binding proteins on bone metabolism regulation. Additionally, we explore the potential and rationale for modulating RNA-binding proteins as a means of treating osteoporosis, with an overview of drugs that target these proteins.
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Affiliation(s)
- Jiaqiang Wu
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, 332000, China; The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Department of General Surgery, First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Liyan Niu
- HuanKui College of Nanchang University, Nanchang 330006, China
| | - Kangping Yang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
| | - Jingdong Xu
- Queen Mary College of Nanchang University, Nanchang 330006, China
| | - Deju Zhang
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, 999077, Hong Kong, China
| | - Jitao Ling
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Panpan Xia
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Yuting Wu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Xiao Liu
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510275, China
| | - Jianping Liu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Jing Zhang
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, 332000, China; Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
| | - Peng Yu
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, 332000, China; Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China.
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14
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Bence M, Jankovics F, Kristó I, Gyetvai Á, Vértessy BG, Erdélyi M. Direct interaction of Su(var)2-10 via the SIM-binding site of the Piwi protein is required for transposon silencing in Drosophila melanogaster. FEBS J 2024; 291:1759-1779. [PMID: 38308815 DOI: 10.1111/febs.17073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 11/30/2023] [Accepted: 01/22/2024] [Indexed: 02/05/2024]
Abstract
Nuclear Piwi/Piwi-interacting RNA complexes mediate co-transcriptional silencing of transposable elements by inducing local heterochromatin formation. In Drosophila, sumoylation plays an essential role in the assembly of the silencing complex; however, the molecular mechanism by which the sumoylation machinery is recruited to the transposon loci is poorly understood. Here, we show that the Drosophila E3 SUMO-ligase Su(var)2-10 directly binds to the Piwi protein. This interaction is mediated by the SUMO-interacting motif-like (SIM-like) structure in the C-terminal domain of Su(var)2-10. We demonstrated that the SIM-like structure binds to a special region found in the MID domain of the Piwi protein, the structure of which is highly similar to the SIM-binding pocket of SUMO proteins. Abrogation of the Su(var)2-10-binding surface of the Piwi protein resulted in transposon derepression in the ovary of adult flies. Based on our results, we propose a model in which the Piwi protein initiates local sumoylation in the silencing complex by recruiting Su(var)2-10 to the transposon loci.
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Affiliation(s)
- Melinda Bence
- Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary
| | - Ferenc Jankovics
- Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary
- Department of Medical Biology, University of Szeged, Hungary
| | - Ildikó Kristó
- Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary
| | - Ákos Gyetvai
- Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary
| | - Beáta G Vértessy
- Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Hungary
- Institute of Enzymology, HUN-REN Research Centre of Natural Sciences, Budapest, Hungary
| | - Miklós Erdélyi
- Institute of Genetics, HUN-REN Biological Research Centre, Szeged, Hungary
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15
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Pastore B, Hertz HL, Tang W. Pre-piRNA trimming safeguards piRNAs against erroneous targeting by RNA-dependent RNA polymerase. Cell Rep 2024; 43:113692. [PMID: 38244197 PMCID: PMC10949418 DOI: 10.1016/j.celrep.2024.113692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/13/2023] [Accepted: 01/04/2024] [Indexed: 01/22/2024] Open
Abstract
The Piwi/Piwi-interacting RNA (piRNA) pathway protects genome integrity in animal germ lines. Maturation of piRNAs involves nucleolytic processing at both 5' and 3' ends. The ribonuclease PARN-1 and its orthologs mediate piRNA 3' trimming in worms, insects, and mammals. However, the significance of this evolutionarily conserved processing step is not fully understood. Employing C. elegans as a model, we recently discovered that 3' trimming protects piRNAs against non-templated nucleotide additions and degradation. Here, we find that worms lacking PARN-1 accumulate an uncharacterized RNA species termed anti-piRNAs, which are antisense to piRNAs. Anti-piRNAs associate with Piwi proteins, are 17-19 nucleotides long, and begin with 5' guanine or adenine. Untrimmed pre-piRNAs are misdirected by the terminal nucleotidyltransferase RDE-3 and RNA-dependent RNA polymerase EGO-1, leading to the formation of anti-piRNAs. This work identifies a class of small RNAs in parn-1 mutants and provides insight into the activities of RDE-3, EGO-1, and Piwi proteins.
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Affiliation(s)
- Benjamin Pastore
- Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA
| | - Hannah L Hertz
- Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA
| | - Wen Tang
- Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA.
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16
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Youness RA, Habashy DA, Khater N, Elsayed K, Dawoud A, Hakim S, Nafea H, Bourquin C, Abdel-Kader RM, Gad MZ. Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review. Noncoding RNA 2024; 10:7. [PMID: 38250807 PMCID: PMC10801522 DOI: 10.3390/ncrna10010007] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 01/07/2024] [Accepted: 01/08/2024] [Indexed: 01/23/2024] Open
Abstract
Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a "Maestro" role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H2S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H2S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders.
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Affiliation(s)
- Rana A. Youness
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
- Biology and Biochemistry Department, Faculty of Biotechnology, German International University (GIU), New Administrative Capital, Cairo 11835, Egypt
| | - Danira Ashraf Habashy
- Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
- Clinical Pharmacy Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Nour Khater
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Kareem Elsayed
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Alyaa Dawoud
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Sousanna Hakim
- Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Heba Nafea
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Carole Bourquin
- School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, 1211 Geneva, Switzerland;
| | - Reham M. Abdel-Kader
- Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - Mohamed Z. Gad
- Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
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17
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Ge QQ, Han Q, Han Y, Ma F, Li CZ, Zhang CY. A multi-cycle signal amplification-mediated single quantum dot nanosensor for PIWI-interacting RNA detection. Chem Commun (Camb) 2024; 60:408-411. [PMID: 38084051 DOI: 10.1039/d3cc05639b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
We construct a single quantum dot-based nanosensor for piRNA detection based on ligation-mediated multi-cycle signal amplification. This nanosensor is homogenous, selective, and sensitive with a detection limit of 0.104 fM. Moreover, it can detect the endogenous piRNA level in different cell lines, and discriminate cancer tissues from normal tissues.
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Affiliation(s)
- Qi-Qin Ge
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
| | - Qian Han
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
| | - Yun Han
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
| | - Fei Ma
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
| | - Chen-Zhong Li
- Biomedical Engineering, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, China.
| | - Chun-Yang Zhang
- School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
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18
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Huang Y, Li Y, Zhang K, Xu J, Li P, Yan X, Sun K. Expression and diagnostic value of PIWI-interacting RNA by serum in acute myocardial infarction. J Cardiol 2023; 82:441-447. [PMID: 37422074 DOI: 10.1016/j.jjcc.2023.06.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 06/13/2023] [Accepted: 06/30/2023] [Indexed: 07/10/2023]
Abstract
OBJECTIVE To detect the expression level of PIWI-interacting RNA in the serum of patients with acute myocardial infarction, and to explore the role of PIWI-interacting RNA in acute myocardial infarction. METHODS RNA was extracted from the serum of acute myocardial infarction patients and healthy subjects, and high-throughput sequencing of PIWI-interacting RNAs was performed to screen differentially expressed PIWI-interacting RNAs. Quantitative polymerase chain reaction was used to detect the expression of four differentially expressed PIWI-interacting RNAs in 52 patients with acute myocardial infarction and 30 healthy people. Receiver operating characteristic (ROC) curve was further used to analyze the correlation between differentially expressed PIWI-interacting RNAs and the occurrence of acute myocardial infarction. Kyoto Encyclopedia of Genes and Genomes analysis was used to analyze the role of PIWI-interacting RNA in the occurrence of acute myocardial infarction. RESULTS RNA sequencing and bioinformatics analysis revealed that most piRNAs were upregulated in AMI patients, with 195 upregulated and 13 downregulated. Among them, piR-hsa-9010, piR-hsa-28646, and piR-hsa-23619 were significantly up-regulated in the serum of patients with acute myocardial infarction, but their expression in the acute heart failure group and coronary heart disease group was not significantly different from that in the healthy group. ROC curve analysis showed that piR-hsa-9010, piR-hsa-28646, and piR-hsa-23619 had high diagnostic values in acute myocardial infarction. In vitro, there was no significant difference in the expression of piR-hsa-9010 among THP-1, HUVEC, and AC16, while the expression of piR-hsa-28646 and piR-hsa-23619 in HUVEC was significantly higher than that in THP-1 and AC16. Pathway analysis showed that piR-hsa-23619 was mainly involved in TNF signaling pathway, and piR-hsa-28646 was mainly involved in Wnt signaling pathway. CONCLUSION piR-hsa-9010, piR-hsa-28646, and piR-hsa-23619 were significantly up-regulated in the serum of patients with acute myocardial infarction. It can be used as a new biomarker for the diagnosis of acute myocardial infarction, which may be a therapeutic target for acute myocardial infarction.
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Affiliation(s)
- Ying Huang
- Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China
| | - Yuan Li
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China
| | - Kaiyu Zhang
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China
| | - Jingyi Xu
- Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China
| | - Ping Li
- Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China
| | - Xinxin Yan
- Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China.
| | - Kangyun Sun
- Department of Cardiology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu 215008, PR China.
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19
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Joshi M, Sethi S, Mehta P, Kumari A, Rajender S. Small RNAs, spermatogenesis, and male infertility: a decade of retrospect. Reprod Biol Endocrinol 2023; 21:106. [PMID: 37924131 PMCID: PMC10625245 DOI: 10.1186/s12958-023-01155-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023] Open
Abstract
Small non-coding RNAs (sncRNAs), being the top regulators of gene expression, have been thoroughly studied in various biological systems, including the testis. Research over the last decade has generated significant evidence in support of the crucial roles of sncRNAs in male reproduction, particularly in the maintenance of primordial germ cells, meiosis, spermiogenesis, sperm fertility, and early post-fertilization development. The most commonly studied small RNAs in spermatogenesis are microRNAs (miRNAs), PIWI-interacting RNA (piRNA), small interfering RNA (siRNA), and transfer RNA-derived small RNAs (ts-RNAs). Small non-coding RNAs are crucial in regulating the dynamic, spatial, and temporal gene expression profiles in developing germ cells. A number of small RNAs, particularly miRNAs and tsRNAs, are loaded on spermatozoa during their epididymal maturation. With regard to their roles in fertility, miRNAs have been studied most often, followed by piRNAs and tsRNAs. Dysregulation of more than 100 miRNAs has been shown to correlate with infertility. piRNA and tsRNA dysregulations in infertility have been studied in only 3-5 studies. Sperm-borne small RNAs hold great potential to act as biomarkers of sperm quality and fertility. In this article, we review the role of small RNAs in spermatogenesis, their association with infertility, and their potential as biomarkers of sperm quality and fertility.
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Affiliation(s)
- Meghali Joshi
- Division of Endocrinology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
| | - Shruti Sethi
- Division of Endocrinology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
| | - Poonam Mehta
- Division of Endocrinology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
| | - Anamika Kumari
- Division of Endocrinology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
| | - Singh Rajender
- Division of Endocrinology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India.
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20
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Huang X, Wang C, Zhang T, Li R, Chen L, Leung KL, Lakso M, Zhou Q, Zhang H, Wong G. PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease. Nat Commun 2023; 14:6137. [PMID: 37783675 PMCID: PMC10545829 DOI: 10.1038/s41467-023-41881-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 09/21/2023] [Indexed: 10/04/2023] Open
Abstract
PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)Tg and AβTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders.
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Affiliation(s)
- Xiaobing Huang
- Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, China
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
| | - Changliang Wang
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
- GMU-GIBH Joint School of Life Sciences, Guangzhou Laboratory, Guangzhou Medical University, Guangzhou, 510799, China
| | - Tianjiao Zhang
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
| | - Rongzhen Li
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
| | - Liang Chen
- Department of Computer Science, College of Engineering, Shantou University, Shantou, 515063, China
| | - Ka Lai Leung
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
| | - Merja Lakso
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
| | - Qinghua Zhou
- Department of Anesthesiology, The First Affiliated Hospital, Jinan University, Guangzhou, 510630, China
- Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, China
| | - Hongjie Zhang
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China
| | - Garry Wong
- Cancer Centre, Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, 999078, Macau, China.
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21
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Podvalnaya N, Bronkhorst AW, Lichtenberger R, Hellmann S, Nischwitz E, Falk T, Karaulanov E, Butter F, Falk S, Ketting RF. piRNA processing by a trimeric Schlafen-domain nuclease. Nature 2023; 622:402-409. [PMID: 37758951 PMCID: PMC10567574 DOI: 10.1038/s41586-023-06588-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023]
Abstract
Transposable elements are genomic parasites that expand within and spread between genomes1. PIWI proteins control transposon activity, notably in the germline2,3. These proteins recognize their targets through small RNA co-factors named PIWI-interacting RNAs (piRNAs), making piRNA biogenesis a key specificity-determining step in this crucial genome immunity system. Although the processing of piRNA precursors is an essential step in this process, many of the molecular details remain unclear. Here, we identify an endoribonuclease, precursor of 21U RNA 5'-end cleavage holoenzyme (PUCH), that initiates piRNA processing in the nematode Caenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain proteins (SLFL proteins), executes 5'-end piRNA precursor cleavage. PUCH-mediated processing strictly requires a 7-methyl-G cap (m7G-cap) and a uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds to piRNA precursors4, and that this interaction enhances piRNA production in vivo. The identification of PUCH concludes the search for the 5'-end piRNA biogenesis factor in C. elegans and uncovers a type of RNA endonuclease formed by three SLFL proteins. Mammalian Schlafen (SLFN) genes have been associated with immunity5, exposing a molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.
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Affiliation(s)
- Nadezda Podvalnaya
- Biology of Non-coding RNA group, Institute of Molecular Biology, Mainz, Germany
- International PhD Programme on Gene Regulation, Epigenetics & Genome Stability, Mainz, Germany
| | - Alfred W Bronkhorst
- Biology of Non-coding RNA group, Institute of Molecular Biology, Mainz, Germany
| | - Raffael Lichtenberger
- Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria
- Department of Structural and Computational Biology, Center for Molecular Biology, University of Vienna, Vienna, Austria
| | - Svenja Hellmann
- Biology of Non-coding RNA group, Institute of Molecular Biology, Mainz, Germany
| | - Emily Nischwitz
- International PhD Programme on Gene Regulation, Epigenetics & Genome Stability, Mainz, Germany
- Quantitative Proteomics group, Institute of Molecular Biology, Mainz, Germany
| | - Torben Falk
- Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria
- Department of Structural and Computational Biology, Center for Molecular Biology, University of Vienna, Vienna, Austria
| | - Emil Karaulanov
- Bioinformatics Core Facility, Institute of Molecular Biology, Mainz, Germany
| | - Falk Butter
- Department of Structural and Computational Biology, Center for Molecular Biology, University of Vienna, Vienna, Austria
- Institute of Molecular Virology and Cell Biology, Friedrich Loeffler Institute, Greifswald, Germany
| | - Sebastian Falk
- Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria.
- Department of Structural and Computational Biology, Center for Molecular Biology, University of Vienna, Vienna, Austria.
| | - René F Ketting
- Biology of Non-coding RNA group, Institute of Molecular Biology, Mainz, Germany.
- Institute of Developmental Biology and Neurobiology, Johannes Gutenberg University, Mainz, Germany.
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22
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Pastore B, Hertz HL, Tang W. Pre-piRNA trimming safeguards piRNAs against erroneous targeting by RNA-dependent RNA Polymerase. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.09.26.559619. [PMID: 37808652 PMCID: PMC10557677 DOI: 10.1101/2023.09.26.559619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2023]
Abstract
In animal germ lines, The Piwi/piRNA pathway plays a crucial role in safeguarding genome integrity and promoting fertility. Following transcription from discrete genomic loci, piRNA precursors undergo nucleolytic processing at both 5' and 3' ends. The ribonuclease PARN-1 and its orthologs mediate piRNA 3' trimming in worms, insects and mammals. Yet, the significance of this evolutionarily conserved processing step is not well understood. Employing C. elegans as a model organism, our recent work has demonstrated that 3' trimming protects piRNAs against non-templated nucleotide additions and degradation. In this study, we present an unexpected finding that C. elegans deficient for PARN-1 accumulate a heretofore uncharacterized RNA species termed anti-piRNAs, which are antisense to piRNAs. These anti-piRNAs associate with Piwi proteins and display the propensity for a length of 17-19 nucleotides and 5' guanine and adenine residues. We show that untrimmed pre-piRNAs in parn-1 mutants are modified by the terminal nucleotidyltransferase RDE-3 and erroneously targeted by the RNA-dependent RNA polymerase EGO-1, thereby giving rise to anti-piRNAs. Taken together, our work identifies a previously unknown class of small RNAs upon loss of parn-1 and provides mechanistic insight to activities of RDE-3, EGO-1 and Piwi proteins.
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23
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Choi Y, Nam MW, Lee HK, Choi KC. Use of cutting-edge RNA-sequencing technology to identify biomarkers and potential therapeutic targets in canine and feline cancers and other diseases. J Vet Sci 2023; 24:e71. [PMID: 38031650 PMCID: PMC10556291 DOI: 10.4142/jvs.23036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 06/16/2023] [Accepted: 06/18/2023] [Indexed: 12/01/2023] Open
Abstract
With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNA-sequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare. Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also non-coding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.
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Affiliation(s)
- Youngdong Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Min-Woo Nam
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Hong Kyu Lee
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Kyung-Chul Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.
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24
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van Wolfswinkel JC. Insights in piRNA targeting rules. WILEY INTERDISCIPLINARY REVIEWS. RNA 2023; 15:e1811. [PMID: 37632327 PMCID: PMC10895071 DOI: 10.1002/wrna.1811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 06/22/2023] [Accepted: 07/06/2023] [Indexed: 08/27/2023]
Abstract
PIWI-interacting RNAs (piRNAs) play an important role in the defense against transposons in the germline and stem cells of animals. To what extent other transcripts are also regulated by piRNAs is an ongoing topic of debate. The amount of sequence complementarity between piRNA and target that is required for effective downregulation of the targeted transcript is guiding in this discussion. Over the years, various methods have been applied to infer targeting requirements from the collections of piRNAs and potential target transcripts, and recent structural studies of the PIWI proteins have provided an additional perspective. In this review, I summarize the findings from these studies and propose a set of requirements that can be used to predict targets to the best of our current abilities. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA-Based Catalysis > RNA-Mediated Cleavage.
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Affiliation(s)
- Josien C van Wolfswinkel
- Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA
- Center for Stem Cell Biology, Yale School of Medicine, New Haven, Connecticut, USA
- Center for RNA Biology and Medicine, Yale School of Medicine, New Haven, Connecticut, USA
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25
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Santiago PB, da Silva Bentes KL, da Silva WMC, Praça YR, Charneau S, Chaouch S, Grellier P, Dos Santos Silva Ferraz MA, Bastos IMD, de Santana JM, de Araújo CN. Insights into the microRNA landscape of Rhodnius prolixus, a vector of Chagas disease. Sci Rep 2023; 13:13120. [PMID: 37573416 PMCID: PMC10423254 DOI: 10.1038/s41598-023-40353-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 08/09/2023] [Indexed: 08/14/2023] Open
Abstract
The growing interest in microRNAs (miRNAs) over recent years has led to their characterization in numerous organisms. However, there is currently a lack of data available on miRNAs from triatomine bugs (Reduviidae: Triatominae), which are the vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. A comprehensive understanding of the molecular biology of vectors provides new insights into insect-host interactions and insect control approaches, which are key methods to prevent disease incidence in endemic areas. In this work, we describe the miRNome profiles from gut, hemolymph, and salivary gland tissues of the Rhodnius prolixus triatomine. Small RNA sequencing data revealed abundant expression of miRNAs, along with tRNA- and rRNA-derived fragments. Fifty-two mature miRNAs, previously reported in Ecdysozoa, were identified, including 39 ubiquitously expressed in the three tissues. Additionally, 112, 73, and 78 novel miRNAs were predicted in the gut, hemolymph, and salivary glands, respectively. In silico prediction showed that the top eight most highly expressed miRNAs from salivary glands potentially target human blood-expressed genes, suggesting that R. prolixus may modulate the host's gene expression at the bite site. This study provides the first characterization of miRNAs in a Triatominae species, shedding light on the role of these crucial regulatory molecules.
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Affiliation(s)
- Paula Beatriz Santiago
- Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, Brazil
| | - Kaio Luís da Silva Bentes
- Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, Brazil
| | | | - Yanna Reis Praça
- Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, Brazil
| | - Sébastien Charneau
- Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, Brazil
| | - Soraya Chaouch
- UMR 7245 Molécules de Communication et Adaptation des Micro-organismes, Muséum National d'Histoire Naturelle, CNRS, CP52, 61 rue Buffon, 0575231, Paris Cedex, France
| | - Philippe Grellier
- UMR 7245 Molécules de Communication et Adaptation des Micro-organismes, Muséum National d'Histoire Naturelle, CNRS, CP52, 61 rue Buffon, 0575231, Paris Cedex, France
| | | | - Izabela Marques Dourado Bastos
- Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, Brazil
| | - Jaime Martins de Santana
- Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, Brazil
| | - Carla Nunes de Araújo
- Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, DF, Brazil.
- Faculty of Ceilândia, University of Brasília, Brasília, DF, Brazil.
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26
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de Carvalho CF. Epigenetic effects of climate change on insects. CURRENT OPINION IN INSECT SCIENCE 2023; 57:101029. [PMID: 37028647 DOI: 10.1016/j.cois.2023.101029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 03/17/2023] [Accepted: 03/30/2023] [Indexed: 05/10/2023]
Abstract
Climate change has been causing severe modifications to the environment that are predicted to aggravate in the future, which create critical challenges for insects to cope. Populations can respond to the changes depending on the standing genetic variation. Additionally, they could potentially rely on epigenetic mechanisms as a source of phenotypic variation. These mechanisms can influence gene regulation and can respond to the external environment, being implicated in phenotypic plasticity. Thus, epigenetic variation could be advantageous in changing, unpredictable environments. However, little is known about causal relationships between epigenetic marks and insects' phenotypes, and whether the effects are truly beneficial to the fitness. Empirical studies are now urgent to better understand whether epigenetic variation can help or hinder insect populations facing climate change.
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Affiliation(s)
- Clarissa F de Carvalho
- Dep. de Ecologia e Biologia Evolutiva, Federal University of São Paulo, Diadema 09972-270, Brazil.
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27
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Behura A, Naik L, Patel S, Das M, Kumar A, Mishra A, Nayak DK, Manna D, Mishra A, Dhiman R. Involvement of epigenetics in affecting host immunity during SARS-CoV-2 infection. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166634. [PMID: 36577469 PMCID: PMC9790847 DOI: 10.1016/j.bbadis.2022.166634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 10/26/2022] [Accepted: 12/13/2022] [Indexed: 12/27/2022]
Abstract
Coronavirus disease 19 (COVID-19) is caused by a highly contagious RNA virus Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), originated in December 2019 in Wuhan, China. Since then, it has become a global public health concern and leads the disease table with the highest mortality rate, highlighting the necessity for a thorough understanding of its biological properties. The intricate interaction between the virus and the host immune system gives rise to diverse implications of COVID-19. RNA viruses are known to hijack the host epigenetic mechanisms of immune cells to regulate antiviral defence. Epigenetics involves processes that alter gene expression without changing the DNA sequence, leading to heritable phenotypic changes. The epigenetic landscape consists of reversible modifications like chromatin remodelling, DNA/RNA methylation, and histone methylation/acetylation that regulates gene expression. The epigenetic machinery contributes to many aspects of SARS-CoV-2 pathogenesis, like global DNA methylation and receptor angiotensin-converting enzyme 2 (ACE2) methylation determines the viral entry inside the host, viral replication, and infection efficiency. Further, it is also reported to epigenetically regulate the expression of different host cytokines affecting antiviral response. The viral proteins of SARS-CoV-2 interact with various host epigenetic enzymes like histone deacetylases (HDACs) and bromodomain-containing proteins to antagonize cellular signalling. The central role of epigenetic factors in SARS-CoV-2 pathogenesis is now exploited as promising biomarkers and therapeutic targets against COVID-19. This review article highlights the ability of SARS-CoV-2 in regulating the host epigenetic landscape during infection leading to immune evasion. It also discusses the ongoing therapeutic approaches to curtail and control the viral outbreak.
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Affiliation(s)
- Assirbad Behura
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Lincoln Naik
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Salina Patel
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Mousumi Das
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Ashish Kumar
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Abtar Mishra
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Dev Kiran Nayak
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Debraj Manna
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Amit Mishra
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan 342011, India
| | - Rohan Dhiman
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India.
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28
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Dowling M, Homolka D, Raad N, Gos P, Pandey RR, Pillai RS. In vivo PIWI slicing in mouse testes deviates from rules established in vitro. RNA (NEW YORK, N.Y.) 2023; 29:308-316. [PMID: 36617658 PMCID: PMC9945443 DOI: 10.1261/rna.079349.122] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 12/02/2022] [Indexed: 06/17/2023]
Abstract
Argonautes are small RNA-binding proteins, with some having small RNA-guided endonuclease (slicer) activity that cleaves target nucleic acids. One cardinal rule that is structurally defined is the inability of slicers to cleave target RNAs when nucleotide mismatches exist between the paired small RNA and the target at the cleavage site. Animal-specific PIWI clade Argonautes associate with PIWI-interacting RNAs (piRNAs) to silence transposable elements in the gonads, and this is essential for fertility. We previously demonstrated that purified endogenous mouse MIWI fails to cleave mismatched targets in vitro. Surprisingly, here we find using knock-in mouse models that target sites with cleavage-site mismatches at the 10th and 11th piRNA nucleotides are precisely sliced in vivo. This is identical to the slicing outcome in knock-in mice where targets are base-paired perfectly with the piRNA. Additionally, we find that pachytene piRNA-guided slicing in both these situations failed to initiate phased piRNA production from the specific target mRNA we studied. Instead, the two slicer cleavage fragments were retained in PIWI proteins as pre-piRNA and 17-19 nt by-product fragments. Our results indicate that PIWI slicing rules established in vitro are not respected in vivo, and that all targets of PIWI slicing are not substrates for piRNA biogenesis.
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Affiliation(s)
- Mark Dowling
- Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland
| | - David Homolka
- Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland
| | - Nicole Raad
- Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland
| | - Pascal Gos
- Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland
| | - Radha Raman Pandey
- Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland
| | - Ramesh S Pillai
- Department of Molecular Biology, University of Geneva, CH-1211 Geneva 4, Switzerland
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29
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Li Y, Hui JHL. Small RNAs in Cnidaria: A review. Evol Appl 2023; 16:354-364. [PMID: 36793685 PMCID: PMC9923473 DOI: 10.1111/eva.13445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 05/18/2022] [Accepted: 06/17/2022] [Indexed: 11/30/2022] Open
Abstract
As fundamental components of RNA silencing, small RNA (sRNA) molecules ranging from 20 to 32 nucleotides in length have been found as potent regulators of gene expression and genome stability in many biological processes of eukaryotes. Three major small RNAs are active in animals, including the microRNA (miRNA), short interfering RNA (siRNA), and PIWI-interacting RNA (piRNA). Cnidarians, the sister group to bilaterians, are at a critical phylogenetic node to better model eukaryotic small RNA pathway evolution. To date, most of our understanding of sRNA regulation and its potential contribution to evolution has been limited to a few triploblastic bilaterian and plant models. The diploblastic nonbilaterians, including the cnidarians, are understudied in this regard. Therefore, this review will present the current-known small RNA information in cnidarians to enhance our understanding of the development of the small RNA pathways in early branch animals.
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Affiliation(s)
- Yiqian Li
- Simon F.S. Li Marine Science Laboratory, State Key Laboratory of Agrobiotechnology, School of Life SciencesThe Chinese University of Hong KongHong Kong CityHong Kong
| | - Jerome H. L. Hui
- Simon F.S. Li Marine Science Laboratory, State Key Laboratory of Agrobiotechnology, School of Life SciencesThe Chinese University of Hong KongHong Kong CityHong Kong
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30
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Zheng K, Zhang XL, Wang L, You ZH, Ji BY, Liang X, Li ZW. SPRDA: a link prediction approach based on the structural perturbation to infer disease-associated Piwi-interacting RNAs. Brief Bioinform 2023; 24:6850564. [PMID: 36445194 DOI: 10.1093/bib/bbac498] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 10/17/2022] [Accepted: 10/19/2022] [Indexed: 11/30/2022] Open
Abstract
piRNA and PIWI proteins have been confirmed for disease diagnosis and treatment as novel biomarkers due to its abnormal expression in various cancers. However, the current research is not strong enough to further clarify the functions of piRNA in cancer and its underlying mechanism. Therefore, how to provide large-scale and serious piRNA candidates for biological research has grown up to be a pressing issue. In this study, a novel computational model based on the structural perturbation method is proposed to predict potential disease-associated piRNAs, called SPRDA. Notably, SPRDA belongs to positive-unlabeled learning, which is unaffected by negative examples in contrast to previous approaches. In the 5-fold cross-validation, SPRDA shows high performance on the benchmark dataset piRDisease, with an AUC of 0.9529. Furthermore, the predictive performance of SPRDA for 10 diseases shows the robustness of the proposed method. Overall, the proposed approach can provide unique insights into the pathogenesis of the disease and will advance the field of oncology diagnosis and treatment.
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Affiliation(s)
- Kai Zheng
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha, 410083, China.,College of Information Science and Engineering, Zaozhuang University, Zaozhuang 277100, China
| | - Xin-Lu Zhang
- Civil Product General Research Institute, The 36th Research Institute of China Electronics Technology Group Corporation, Jiaxing, 314000, China
| | - Lei Wang
- College of Information Science and Engineering, Zaozhuang University, Zaozhuang 277100, China.,Big Data and Intelligent Computing Research Center, Guangxi Academy of Sciences, Nanning, 530007, China
| | - Zhu-Hong You
- Big Data and Intelligent Computing Research Center, Guangxi Academy of Sciences, Nanning, 530007, China
| | - Bo-Ya Ji
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, 410006, China
| | - Xiao Liang
- Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, Changsha, 410083, China
| | - Zheng-Wei Li
- College of Information Science and Engineering, Zaozhuang University, Zaozhuang 277100, China.,Big Data and Intelligent Computing Research Center, Guangxi Academy of Sciences, Nanning, 530007, China
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31
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Ray SK, Mukherjee S. Piwi-interacting RNAs (piRNAs) and Colorectal Carcinoma: Emerging Non-invasive diagnostic Biomarkers with Potential Therapeutic Target Based Clinical Implications. Curr Mol Med 2023; 23:300-311. [PMID: 35068393 DOI: 10.2174/1566524022666220124102616] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 11/25/2021] [Accepted: 11/30/2021] [Indexed: 11/22/2022]
Abstract
PIWI-interacting RNAs (piRNAs) constitute new small non-coding RNA molecules of around 24-31 nucleotides in length, mostly performing regulatory roles for the piwi protein family members. In recent times, developing evidence proposes that piRNAs are expressed in a tissue-specific way in various human tissues and act as moderate vital signalling pathways at the transcriptional or post-transcriptional level in addition to mammalian germline. Recent findings, however, show that the unusual expression of piRNAs is an exclusive and discrete feature in several diseases, including many human cancers. Recently, considerable evidence indicates that piRNAs could be dysregulated thus playing critical roles in tumorigenesis. The function and underlying mechanisms of piRNAs in cancer, particularly in colorectal carcinoma, are not fully understood to date. Abnormal expression of piRNAs is emerging as a critical player in cancer cell proliferation, apoptosis, invasion, and migration in vitro and in vivo. Functionally, piRNAs preserve genomic integrity and regulate the expression of downstream target genes through transcriptional or post-transcriptional mechanisms by repressing transposable elements' mobilization. However, little research has been done to check Piwi and piRNAs' potential role in cancer and preserve genome integrity by epigenetically silencing transposons via DNA methylation, especially in germline cancer stem cells. This review reveals emerging insights into piRNA functions in colorectal carcinoma, revealing novel findings behind various piRNA-mediated gene regulation mechanisms, biogenetic piRNA processes, and possible applications of piRNAs and piwi proteins in cancer diagnosis and their potential clinical significance in the treatment of colorectal carcinoma patients.
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Affiliation(s)
| | - Sukhes Mukherjee
- Associate Professor, Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh-462020, India
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32
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Pantazi P, Clements T, Venø M, Abrahams VM, Holder B. Distinct non-coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages. J Extracell Vesicles 2022; 11:e12293. [PMID: 36544271 PMCID: PMC9772496 DOI: 10.1002/jev2.12293] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 11/13/2022] [Accepted: 12/07/2022] [Indexed: 12/24/2022] Open
Abstract
Macrophages are important antigen presenting cells which can release extracellular vesicles (EVs) carrying functional cargo including non-coding RNAs. Macrophages can be broadly classified into M1 'classical' and M2 'alternatively-activated' macrophages. M1 macrophages have been linked with inflammation-associated pathologies, whereas a switch towards an M2 phenotype indicates resolution of inflammation and tissue regeneration. Here, we provide the first comprehensive analysis of the small RNA cargo of EVs from human M1 and M2 primary macrophages. Using small RNA sequencing, we identified several types of small non-coding RNAs in M1 and M2 macrophage EVs including miRNAs, isomiRs, tRNA fragments, piRNA, snRNA, snoRNA and Y-RNA fragments. Distinct differences were observed between M1 and M2 EVs, with higher relative abundance of miRNAs, and lower abundance of tRNA fragments in M1 compared to M2 EVs. MicroRNA-target enrichment analysis identified several gene targets involved in gene expression and inflammatory signalling pathways. EVs were also enriched in tRNA fragments, primarily originating from the 5' end or the internal region of the full length tRNAs, many of which were differentially abundant in M1 and M2 EVs. Similarly, several other small non-coding RNAs, namely snRNAs, snoRNAs and Y-RNA fragments, were differentially enriched in M1 and M2 EVs; we discuss their putative roles in macrophage EVs. In conclusion, we show that M1 and M2 macrophages release EVs with distinct RNA cargo, which has the potential to contribute to the unique effect of these cell subsets on their microenvironment.
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Affiliation(s)
- Paschalia Pantazi
- Institute of Reproductive and Developmental BiologyDepartment of Metabolism, Digestion, and ReproductionImperial College LondonLondonUK
| | - Toby Clements
- Institute of Reproductive and Developmental BiologyDepartment of Metabolism, Digestion, and ReproductionImperial College LondonLondonUK
| | | | - Vikki M. Abrahams
- Department of ObstetricsGynecology and Reproductive SciencesYale School of MedicineNew HavenConnecticutUSA
| | - Beth Holder
- Institute of Reproductive and Developmental BiologyDepartment of Metabolism, Digestion, and ReproductionImperial College LondonLondonUK
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Mai D, Ye Y, Zhuang L, Zheng J, Lin D. Detection of piRNA-54265 in human serum: evidence and significance. Cancer Commun (Lond) 2022; 43:276-279. [PMID: 36336968 PMCID: PMC9926952 DOI: 10.1002/cac2.12381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 09/09/2022] [Accepted: 10/20/2022] [Indexed: 11/09/2022] Open
Affiliation(s)
- Dongmei Mai
- Department of Experimental ResearchSun Yat‐sen University Cancer CenterState Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer MedicineGuangzhouGuangdong510060P. R. China
| | - Ying Ye
- Department of Experimental ResearchSun Yat‐sen University Cancer CenterState Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer MedicineGuangzhouGuangdong510060P. R. China
| | - Lisha Zhuang
- Department of Experimental ResearchSun Yat‐sen University Cancer CenterState Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer MedicineGuangzhouGuangdong510060P. R. China
| | - Jian Zheng
- Department of Experimental ResearchSun Yat‐sen University Cancer CenterState Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer MedicineGuangzhouGuangdong510060P. R. China
| | - Dongxin Lin
- Department of Experimental ResearchSun Yat‐sen University Cancer CenterState Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer MedicineGuangzhouGuangdong510060P. R. China,Department of Etiology and CarcinogenesisNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021P. R. China
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Lv Y, Lu G, Cai Y, Su R, Liang L, Wang X, Mu W, He X, Huang T, Ma J, Zhao Y, Chen ZJ, Xue Y, Liu H, Chan WY. RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits. Protein Cell 2022; 14:51-63. [PMID: 36726756 PMCID: PMC9871953 DOI: 10.1093/procel/pwac040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 08/21/2022] [Indexed: 02/04/2023] Open
Abstract
RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
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Affiliation(s)
| | | | | | | | - Liang Liang
- Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Xin Wang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China
| | - Wenyu Mu
- Center for Reproductive Medicine, Shandong University, Jinan 250012, China,Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China
| | - Xiuqing He
- Center for Reproductive Medicine, Shandong University, Jinan 250012, China,Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China
| | - Tao Huang
- Center for Reproductive Medicine, Shandong University, Jinan 250012, China,Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China
| | - Jinlong Ma
- Center for Reproductive Medicine, Shandong University, Jinan 250012, China,CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China,Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China
| | - Yueran Zhao
- Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250012, China,Center for Reproductive Medicine, Shandong University, Jinan 250012, China,Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China
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Li C, Zhang R, Zhang Z, Ren C, Wang X, He X, Mwacharo JM, Zhang X, Zhang J, Di R, Chu M. Expression characteristics of piRNAs in ovine luteal phase and follicular phase ovaries. Front Vet Sci 2022; 9:921868. [PMID: 36157184 PMCID: PMC9493120 DOI: 10.3389/fvets.2022.921868] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
PIWI-interacting RNAs (piRNAs), as a novel class of small non-coding RNAs that have been shown to be indispensable in germline integrity and stem cell development. However, the expressed characteristics and regulatory roles of piRNAs during different reproductive phases of animals remain unknown. In this study, we investigated the piRNAs expression profiles in ovaries of sheep during the luteal phase (LP) and follicular phase (FP) using the Solexa sequencing technique. A total of 85,219 and 1,27,156 piRNAs tags were identified in ovine ovaries across the two phases. Most expressed piRNAs start with uracil. piRNAs with a length of 24 nt or 27–29 nts accounted for the largest proportion. The obvious ping-pong signature appeared in the FP ovary. The piRNA clusters in the sheep ovary were unevenly distributed on the chromosomes, with high density on Chr 3 and 1. For genome distribution, piRNAs in sheep ovary were mainly derived from intron, CDS, and repeat sequence regions. Compared to the LP ovary, a greater number of expressed piRNA clusters were detected in the FP ovary. Simultaneously, we identified 271 differentially expressed (DE) piRNAs between LP and FP ovaries, with 96 piRNAs upregulated and 175 piRNAs downregulated, respectively. Functional enrichment analysis (GO and KEGG) indicated that their target genes were enriched in reproduction-related pathways including oocyte meiosis, PI3K-Akt, Wnt, and TGF-β signaling pathways. Together, our results highlighted the sequence and expression characteristics of the piRNAs in the sheep ovary, which will help us understand the roles of piRNAs in the ovine estrus cycle.
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Affiliation(s)
- Chunyan Li
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Rensen Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Zijun Zhang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Chunhuan Ren
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Xiangyu Wang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Xiaoyun He
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Joram Mwashigadi Mwacharo
- Small Ruminant Genomics, International Center for Agricultural Research in the Dry Areas (ICARDA), Addis Ababa, Ethiopia
- Institute of Animal and Veterinary Sciences, Animal and Veterinary Sciences, SRUC and Center for Tropical Livestock Genetics and Health (CTLGH), Midlothian, United Kingdom
| | | | - Jinlong Zhang
- Tianjin Institute of Animal Sciences, Tianjin, China
| | - Ran Di
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
- *Correspondence: Ran Di
| | - Mingxing Chu
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
- Mingxing Chu
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36
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Zhan L, Chen M, Pang T, Li X, Long L, Liang D, Peng L, Sun W, Xu E. Attenuation of Piwil2 induced by hypoxic postconditioning prevents cerebral ischemic injury by inhibiting CREB2 promoter methylation. Brain Pathol 2022; 33:e13109. [PMID: 35794855 PMCID: PMC9836370 DOI: 10.1111/bpa.13109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 06/24/2022] [Indexed: 01/24/2023] Open
Abstract
Epigenetic modification contributes to the pathogenesis of cerebral ischemia. Piwil2 belongs to the PIWI proteins subfamily and has a key role in the regulation of gene transcription through epigenetics. However, the roles of Piwil2 in cerebral ischemia have not been investigated. In this study, we aim to elucidate the roles and the underlying molecular mechanisms of Piwil2 in ischemic tolerance induced by hypoxic postconditioning (HPC) against transient global cerebral ischemia (tGCI). We found that the expression of Piwil2 in CA1 was downregulated by HPC after tGCI. Silencing Piwil2 with antisense oligodeoxynucleotide (AS-ODN) in CA1 after tGCI decreased the expression of apoptosis-related proteins and exerted neuroprotective effects. Opposite results were observed after overexpression of Piwil2 induced by administration of Piwil2-carried lentivirus. Furthermore, we revealed differentially expressed Piwil2-interacting piRNAs in CA1 between HPC and tGCI groups by RNA binding protein immunoprecipitation (RIP) assay. Moreover, downregulating Piwil2 induced by HPC or AS-ODN after tGCI caused a marked reduction of DNA methyltransferase 3A (DNMT3A), which in turn abolished the tGCI-induced increase in the DNA methylation of cyclic AMP response element-binding 2 (CREB2), thus increasing mRNA and protein of CREB2. Finally, downregulating Piwil2 restored dendritic complexity and length, prevented the loss of dentritic spines, thereby improving cognitive function after tGCI. These data firstly reveal that Piwil2 plays an important part in HPC-mediated neuroprotection against cerebral ischemia through epigenetic regulation of CREB2.
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Affiliation(s)
- Lixuan Zhan
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - Meiyan Chen
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - Taoyan Pang
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - Xinyu Li
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - Long Long
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - Donghai Liang
- Department of Environmental Health Sciences, Rollins School of Public HealthEmory UniversityAtlantaGeorgiaUSA
| | - Linhui Peng
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - Weiwen Sun
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
| | - En Xu
- Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhouChina
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37
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Unraveling mitochondrial piRNAs in mouse embryonic gonadal cells. Sci Rep 2022; 12:10730. [PMID: 35750721 PMCID: PMC9232517 DOI: 10.1038/s41598-022-14414-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 05/18/2022] [Indexed: 11/08/2022] Open
Abstract
Although mitochondria are widely studied organelles, the recent interest in the role of mitochondrial small noncoding RNAs (sncRNAs), miRNAs, and more recently, piRNAs, is providing new functional perspectives in germ cell development and differentiation. piRNAs (PIWI-interacting RNAs) are single-stranded sncRNAs of mostly about 20-35 nucleotides, generated from the processing of pre-piRNAs. We leverage next-generation sequencing data obtained from mouse primordial germ cells and somatic cells purified from early-differentiating embryonic ovaries and testis from 11.5 to 13.5 days postcoitum. Using bioinformatic tools, we elucidate (i) the origins of piRNAs as transcribed from mitochondrial DNA fragments inserted in the nucleus or from the mitochondrial genome; (ii) their levels of expression; and (iii) their potential roles, as well as their association with genomic regions encoding other sncRNAs (such as tRNAs and rRNAs) and the mitochondrial regulatory region (D-loop). Finally, our results suggest how nucleo-mitochondrial communication, both anterograde and retrograde signaling, may be mediated by mitochondria-associated piRNAs.
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38
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Liao W, Du J, Wang Z, Feng Q, Liao M, Liu H, Yuan K, Zeng Y. The role and mechanism of noncoding RNAs in regulation of metabolic reprogramming in hepatocellular carcinoma. Int J Cancer 2022; 151:337-347. [PMID: 35460073 PMCID: PMC9325518 DOI: 10.1002/ijc.34040] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/24/2022] [Accepted: 04/05/2022] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Metabolic reprogramming is considered to be an important hallmark of cancer. Emerging studies have demonstrated that noncoding RNAs (ncRNAs) are closely associated with metabolic reprogramming of HCC. NcRNAs can directly regulate the expressions or functions of metabolic enzymes or indirectly regulate the metabolism of HCC cells through some vital signaling pathways. Until now, the mechanisms of HCC development and progression remain largely unclear, and understanding the regulatory mechanism of ncRNAs on metabolic reprogramming of HCC may provide an important basis for breakthrough progress in the treatment of HCC. In this review, we summarize the ncRNAs involved in regulating metabolic reprogramming of HCC. Specifically, the regulatory roles of ncRNAs in glucose, lipid and amino acid metabolism are elaborated. In addition, we discuss the molecular mechanism of ncRNAs in regulation of metabolic reprogramming and possible therapeutic strategies that target the metabolism of cancer cells by modulating the expressions of specific ncRNAs.
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Affiliation(s)
- Wenwei Liao
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Jinpeng Du
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Zhen Wang
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Qingbo Feng
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Mingheng Liao
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Huixian Liu
- Department of Postanesthesia Care Unit & Surgical Anesthesia Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kefei Yuan
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yong Zeng
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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Cai A, Hu Y, Zhou Z, Qi Q, Wu Y, Dong P, Chen L, Wang F. PIWI-Interacting RNAs (piRNAs): Promising Applications as Emerging Biomarkers for Digestive System Cancer. Front Mol Biosci 2022; 9:848105. [PMID: 35155584 PMCID: PMC8829394 DOI: 10.3389/fmolb.2022.848105] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 01/12/2022] [Indexed: 12/24/2022] Open
Abstract
PIWI-interacting RNAs (piRNAs) are a novel type of small non-coding RNAs (sncRNAs), which are 26–31 nucleotides in length and bind to PIWI proteins. Although piRNAs were originally discovered in germline cells and are thought to be essential regulators for germline preservation, they can also influence gene expression in somatic cells. An increasing amount of data has shown that the dysregulation of piRNAs can both promote and repress the emergence and progression of human cancers through DNA methylation, transcriptional silencing, mRNA turnover, and translational control. Digestive cancers are currently a major cause of cancer deaths worldwide. piRNAs control the expression of essential genes and pathways associated with digestive cancer progression and have been reported as possible biomarkers for the diagnosis and treatment of digestive cancer. Here, we highlight recent advances in understanding the involvement of piRNAs, as well as potential diagnostic and therapeutic applications of piRNAs in various digestive cancers.
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Affiliation(s)
- Aiting Cai
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Yuhao Hu
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Zhou Zhou
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Qianyi Qi
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Yixuan Wu
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Peixin Dong
- Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido University, Sapporo, Japan
- *Correspondence: Peixin Dong, ; Lin Chen, ; Feng Wang,
| | - Lin Chen
- Department of Gastroenterology and Laboratory Medicine, Nantong Third Hospital Affiliated to Nantong University, Nantong, China
- *Correspondence: Peixin Dong, ; Lin Chen, ; Feng Wang,
| | - Feng Wang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
- *Correspondence: Peixin Dong, ; Lin Chen, ; Feng Wang,
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Abstract
Increasing evidence indicates that non-DNA sequence-based epigenetic information can be inherited across several generations in organisms ranging from yeast to plants to humans. This raises the possibility of heritable 'epimutations' contributing to heritable phenotypic variation and thus to evolution. Recent work has shed light on both the signals that underpin these epimutations, including DNA methylation, histone modifications and non-coding RNAs, and the mechanisms by which they are transmitted across generations at the molecular level. These mechanisms can vary greatly among species and have a more limited effect in mammals than in plants and other animal species. Nevertheless, common principles are emerging, with transmission occurring either via direct replicative mechanisms or indirect reconstruction of the signal in subsequent generations. As these processes become clearer we continue to improve our understanding of the distinctive features and relative contribution of DNA sequence and epigenetic variation to heritable differences in phenotype.
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Pastore B, Hertz HL, Tang W. Comparative analysis of piRNA sequences, targets and functions in nematodes. RNA Biol 2022; 19:1276-1292. [PMID: 36412988 PMCID: PMC9683057 DOI: 10.1080/15476286.2022.2149170] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Piwi proteins and Piwi-interacting RNAs (piRNAs) are best known for their roles in suppressing transposons and promoting fertility. Yet piRNA biogenesis and its mechanisms of action differ widely between distantly related species. To better understand the evolution of piRNAs, we characterized the piRNA pathway in C. briggsae, a sibling species of the model organism C. elegans. Our analyses define 25,883 piRNA producing-loci in C. briggsae. piRNA sequences in C. briggsae are extremely divergent from their counterparts in C. elegans, yet both species adopt similar genomic organization that drive piRNA expression. By examining production of Piwi-mediated secondary small RNAs, we identified a set of protein-coding genes that are evolutionarily conserved piRNA targets. In contrast to C. elegans, small RNAs targeting ribosomal RNAs or histone transcripts are not hyper-accumulated in C. briggsae Piwi mutants. Instead, we found that transcripts with few introns are prone to small RNA overamplification. Together our work highlights evolutionary conservation and divergence of the nematode piRNA pathway and provides insights into its role in endogenous gene regulation.
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Affiliation(s)
- Benjamin Pastore
- Department of Biological Chemistry and Pharmacology, The Ohio State University,Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, USA,Center for RNA Biology, Ohio State University, Columbus, OH, USA
| | - Hannah L. Hertz
- Department of Biological Chemistry and Pharmacology, The Ohio State University,Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, USA
| | - Wen Tang
- Department of Biological Chemistry and Pharmacology, The Ohio State University,Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, USA,CONTACT Wen Tang Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA
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42
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Mokarram P, Niknam M, Sadeghdoust M, Aligolighasemabadi F, Siri M, Dastghaib S, Brim H, Ashktorab H. PIWI interacting RNAs perspectives: a new avenues in future cancer investigations. Bioengineered 2021; 12:10401-10419. [PMID: 34723746 PMCID: PMC8809986 DOI: 10.1080/21655979.2021.1997078] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
As a currently identified small non-coding RNAs (ncRNAs) category, the PIWI-interacting RNAs (piRNAs) are crucial mediators of cell biology. The human genome comprises over 30.000 piRNA genes. Although considered a new field in cancer research, the piRNA pathway is shown by the existing evidence as an active pathway in a variety of different types of cancers with critical impacts on main aspects of cancer progression. Among the regulatory molecules that contribute to maintaining the dynamics of cancer cells, the P-element Induced WImpy testis (PIWI) proteins and piRNAs, as new players, have not been broadly studied so far. Therefore, the identification of cancer-related piRNAs and the assessment of target genes of piRNAs may lead to better cancer prevention and therapy strategies. This review articleaimed to highlight the role and function of piRNAs based on existing data. Understanding the role of piRNA in cancer may provide perspectives on their applications as particular biomarker signature in diagnosis in early stage, prognosis and therapeutic strategies.
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Affiliation(s)
- Pooneh Mokarram
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran,Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran,CONTACT Pooneh Mokarram Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Niknam
- Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammadamin Sadeghdoust
- Department of Internal Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran
| | - Farnaz Aligolighasemabadi
- Department of Internal Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran
| | - Morvarid Siri
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sanaz Dastghaib
- Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hassan Brim
- Pathology and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Hassan Ashktorab
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, Dc, USA
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43
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Chen G, Wang S, Long C, Wang Z, Chen X, Tang W, He X, Bao Z, Tan B, Lu WW, Li Z, Yang D, Xiao G, Peng S. PiRNA-63049 inhibits bone formation through Wnt/β-catenin signaling pathway. Int J Biol Sci 2021; 17:4409-4425. [PMID: 34803507 PMCID: PMC8579447 DOI: 10.7150/ijbs.64533] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/13/2021] [Indexed: 12/16/2022] Open
Abstract
Bone remodeling is a dynamic process between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disrupted bone remodeling is a key factor in postmenopausal osteoporosis, a metabolic disorder characterized by deteriorated bone microarchitecture and increased risk of fracture. Recent studies have shown that piwi-binding RNA (piRNA) is involved in the pathogenesis of certain diseases at the post-transcriptional level. Here, we analyzed piRNA-63049 (piR-63049), which may play an essential role in bone remodeling. The expression of piR-63049 significantly increased in both bone tissues and plasma of osteoporotic rats and postmenopausal osteoporotic patients. Overexpressing piR-63049 could inhibit the osteoblastogenesis of bone marrow stromal cells (BMSCs) while knocking down piR-63049 could promote the osteoblastogenesis of BMSCs through the Wnt2b/β-catenin signaling pathway. Moreover, knocking-down piR-63049 (piR-63049-antagonist) in vivo could attenuate the bone loss in ovariectomized rats by promoting bone formation. Taken together, the current study shows that piR-63049 inhibits bone formation through the Wnt2b/β-catenin signaling pathway. This novel piRNA may be a potential target to increase bone formation in bone loss disorders such as postmenopausal osteoporosis.
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Affiliation(s)
- Gaoyang Chen
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Shang Wang
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Canling Long
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Zhenmin Wang
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Xin Chen
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Wanze Tang
- The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Xiaoqin He
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Zhiteng Bao
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Baoyu Tan
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - William W Lu
- Department of Orthopaedic and Traumatology, The University of Hong Kong, Hong Kong, 999077 China
| | - Zhizhong Li
- The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Dazhi Yang
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
| | - Guozhi Xiao
- School of Medicine, Southern University of Science and Technology, Guangdong, Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, China
| | - Songlin Peng
- Department of Spine Surgery, the Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen 518020, China.,The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen 518055, China
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44
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To export, or not to export: how nuclear export factor variants resolve Piwi's dilemma. Biochem Soc Trans 2021; 49:2073-2079. [PMID: 34643228 DOI: 10.1042/bst20201171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 09/06/2021] [Accepted: 09/15/2021] [Indexed: 11/17/2022]
Abstract
Piwi-interacting RNAs (piRNAs) defend animal gonads by guiding PIWI-clade Argonaute proteins to silence transposons. The nuclear Piwi/piRNA complexes confer transcriptional repression of transposons, which is accompanied with heterochromatin formation at target loci. On the other hand, piRNA clusters, genomic loci that transcribe piRNA precursors composed of transposon fragments, are often recognized by piRNAs to define their heterochromatic identity. Therefore, Piwi/piRNA complexes must resolve this conundrum of silencing transposons while allowing the expression of piRNA precursors, at least in Drosophila germlines. This review is focused on recent advances how the piRNA pathway deals with this genetic conflict.
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45
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Shukla A, Perales R, Kennedy S. piRNAs coordinate poly(UG) tailing to prevent aberrant and perpetual gene silencing. Curr Biol 2021; 31:4473-4485.e3. [PMID: 34428467 DOI: 10.1016/j.cub.2021.07.076] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 06/03/2021] [Accepted: 07/28/2021] [Indexed: 11/16/2022]
Abstract
Noncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of such RNA-directed TEI is the inheritance of gene-silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite the self-perpetuating nature of pUG RNA/siRNA cycling, RNAi inheritance is finite, suggesting that systems likely exist to prevent indefinite RNAi-triggered gene silencing. Here we show that, in the absence of Piwi-interacting RNAs (piRNAs), an animal-specific class of small noncoding RNA, RNAi-based gene silencing can become essentially permanent, lasting at near 100% penetrance for more than 5 years and hundreds of generations. This perpetual gene silencing is mediated by continuous pUG RNA/siRNA cycling. Further, we find that piRNAs coordinate endogenous RNAi pathways to prevent germline-expressed genes, which are not normally subjected to TEI, from entering a state of continual and irreversible epigenetic silencing also mediated by continuous maintenance of pUG RNA/siRNA cycling. Together, our results show that one function of C. elegans piRNAs is to insulate germline-expressed genes from aberrant and runaway inactivation by the pUG RNA/siRNA epigenetic inheritance system.
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Affiliation(s)
- Aditi Shukla
- Department of Genetics, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
| | - Roberto Perales
- Department of Genetics, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA; Shape Therapeutics, Seattle, WA 98109, USA
| | - Scott Kennedy
- Department of Genetics, Blavatnik Institute at Harvard Medical School, Boston, MA 02115, USA.
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46
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Li D, Taylor DH, van Wolfswinkel JC. PIWI-mediated control of tissue-specific transposons is essential for somatic cell differentiation. Cell Rep 2021; 37:109776. [PMID: 34610311 PMCID: PMC8532177 DOI: 10.1016/j.celrep.2021.109776] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 07/27/2021] [Accepted: 09/07/2021] [Indexed: 12/24/2022] Open
Abstract
PIWI proteins are known as mediators of transposon silencing in animal germlines but are also found in adult pluripotent stem cells of highly regenerative animals, where they are essential for regeneration. Study of the nuclear PIWI protein SMEDWI-2 in the planarian somatic stem cell system reveals an intricate interplay between transposons and cell differentiation in which a subset of transposons is inevitably activated during cell differentiation, and the PIWI protein is required to regain control. Absence of SMEDWI-2 leads to tissue-specific transposon derepression related to cell-type-specific chromatin remodeling events and in addition causes reduced accessibility of lineage-specific genes and defective cell differentiation, resulting in fatal tissue dysfunction. Finally, we show that additional PIWI proteins provide a stem-cell-specific second layer of protection in planarian neoblasts. These findings reveal a far-reaching role of PIWI proteins and PIWI-interacting RNAs (piRNAs) in stem cell biology and cell differentiation.
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Affiliation(s)
- Danyan Li
- Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA
| | - David H Taylor
- Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA
| | - Josien C van Wolfswinkel
- Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
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Wang X, Zeng C, Liao S, Zhu Z, Zhang J, Tu X, Yao X, Feng X, Guang S, Xu C. Molecular basis for PICS-mediated piRNA biogenesis and cell division. Nat Commun 2021; 12:5595. [PMID: 34552083 PMCID: PMC8458385 DOI: 10.1038/s41467-021-25896-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 09/02/2021] [Indexed: 11/12/2022] Open
Abstract
By incorporating two mutually exclusive factors, PID-1 and TOST-1, C. elegans PICS complex plays important roles in piRNA biogenesis, chromosome segregation and cell division. We firstly map the interaction network between PICS subunits, then uncover the mechanisms underlying the interactions between PICS subunits by solving several complex structures, including those of TOFU-6/PICS-1, ERH-2/PICS-1, and ERH-2/TOST-1. Our biochemical experiment also demonstrates that PICS exists as an octamer consisting of two copies of each subunit. Combining structural analyses with mutagenesis experiments, we identify interfacial residues of PICS subunits that are critical for maintaining intact PICS complex in vitro. Furthermore, using genetics, cell biology and imaging experiments, we find that those mutants impairing the in vitro interaction network within PICS, also lead to dysfunction of PICS in vivo, including mislocalization of PICS, and reduced levels of piRNAs or aberrant chromosome segregation and cell division. Therefore, our work provides structural insights into understanding the PICS-mediated piRNA biogenesis and cell division.
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Affiliation(s)
- Xiaoyang Wang
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Chenming Zeng
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Shanhui Liao
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Zhongliang Zhu
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Jiahai Zhang
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Xiaoming Tu
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Xuebiao Yao
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China
| | - Xuezhu Feng
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.
| | - Shouhong Guang
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.
| | - Chao Xu
- Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, PR China.
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Perez-Borrajero C, Podvalnaya N, Holleis K, Lichtenberger R, Karaulanov E, Simon B, Basquin J, Hennig J, Ketting RF, Falk S. Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans. Genes Dev 2021; 35:1304-1323. [PMID: 34413138 PMCID: PMC8415317 DOI: 10.1101/gad.348648.121] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 07/21/2021] [Indexed: 01/07/2023]
Abstract
In this study, Perez-Borrajero et al. set out to characterize PETISCO architecture and its interaction with RNA, together with its effector proteins TOST-1 and PID-1. Using biochemical and structural biology approaches, the authors found that PETISCO forms a dimer of tetramers, in which dimerization is mediated by both PID-3 and ERH-2. Crystal structures of the PID- 3/TOFU-6 and ERH-2/PID-3 subcomplexes reveal insights into PETISCO assembly, function, and subcellular localization. Using NMR spectroscopy, the authors also characterize the mutually exclusive interplay of ERH-2 with the two effector proteins TOST-1 and PID-1. Piwi-interacting RNAs (piRNAs) constitute a class of small RNAs that bind PIWI proteins and are essential to repress transposable elements in the animal germline, thereby promoting genome stability and maintaining fertility. C. elegans piRNAs (21U RNAs) are transcribed individually from minigenes as precursors that require 5′ and 3′ processing. This process depends on the PETISCO complex, consisting of four proteins: IFE-3, TOFU-6, PID-3, and ERH-2. We used biochemical and structural biology approaches to characterize the PETISCO architecture and its interaction with RNA, together with its effector proteins TOST-1 and PID-1. These two proteins define different PETISCO functions: PID-1 governs 21U processing, whereas TOST-1 links PETISCO to an unknown process essential for early embryogenesis. Here, we show that PETISCO forms an octameric assembly with each subunit present in two copies. Determination of structures of the TOFU-6/PID-3 and PID-3/ERH-2 subcomplexes, supported by in vivo studies of subunit interaction mutants, allows us to propose a model for the formation of the TOFU-6/PID-3/ERH-2 core complex and its functionality in germ cells and early embryos. Using NMR spectroscopy, we demonstrate that TOST-1 and PID-1 bind to a common surface on ERH-2, located opposite its PID-3 binding site, explaining how PETISCO can mediate different cellular roles.
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Affiliation(s)
- Cecilia Perez-Borrajero
- Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany
| | - Nadezda Podvalnaya
- Biology of Noncoding RNA Group, Institute of Molecular Biology, 55128 Mainz, Germany.,International PhD Programme on Gene Regulation, Epigenetics and Genome Stability, 55099 Mainz, Germany
| | - Kay Holleis
- Department of Structural and Computational Biology, Max Perutz Laboratories, University of Vienna, 1030 Vienna, Austria
| | - Raffael Lichtenberger
- Department of Structural and Computational Biology, Max Perutz Laboratories, University of Vienna, 1030 Vienna, Austria
| | - Emil Karaulanov
- Bioinformatics Core Facility, Institute of Molecular Biology, 55099 Mainz, Germany
| | - Bernd Simon
- Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany
| | - Jérôme Basquin
- Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany
| | - Janosch Hennig
- Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany.,Chair of Biochemistry IV, Biophysical Chemistry, University of Bayreuth, 95447 Bayreuth, Germany
| | - René F Ketting
- Biology of Noncoding RNA Group, Institute of Molecular Biology, 55128 Mainz, Germany.,Institute of Developmental Biology and Neurobiology, Johannes Gutenberg University, 55099 Mainz, Germany
| | - Sebastian Falk
- Department of Structural and Computational Biology, Max Perutz Laboratories, University of Vienna, 1030 Vienna, Austria
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Pastore B, Hertz HL, Price IF, Tang W. pre-piRNA trimming and 2'-O-methylation protect piRNAs from 3' tailing and degradation in C. elegans. Cell Rep 2021; 36:109640. [PMID: 34469728 PMCID: PMC8459939 DOI: 10.1016/j.celrep.2021.109640] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 06/24/2021] [Accepted: 08/10/2021] [Indexed: 11/30/2022] Open
Abstract
The Piwi-interacting RNA (piRNA) pathway suppresses transposable elements and promotes fertility in diverse organisms. Maturation of piRNAs involves pre-piRNA trimming followed by 2'-O-methylation at their 3' termini. Here, we report that the 3' termini of Caenorhabditis elegans piRNAs are subject to nontemplated nucleotide addition, and piRNAs with 3' addition exhibit extensive base-pairing interaction with their target RNAs. Animals deficient for PARN-1 (pre-piRNA trimmer) and HENN-1 (2'-O-methyltransferase) accumulate piRNAs with 3' nontemplated nucleotides. In henn-1 mutants, piRNAs are shortened prior to 3' addition, whereas long isoforms of untrimmed piRNAs are preferentially modified in parn-1 mutant animals. Loss of either PARN-1 or HENN-1 results in modest reduction in steady-state levels of piRNAs. Deletion of both enzymes leads to depletion of piRNAs, desilenced piRNA targets, and impaired fecundity. Together, our findings suggest that pre-piRNA trimming and 2'-O-methylation act collaboratively to protect piRNAs from tailing and degradation.
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Affiliation(s)
- Benjamin Pastore
- Department of Biological Chemistry and Pharmacology, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Ohio State Biochemistry Program, Columbus, OH 43210, USA
| | - Hannah L Hertz
- Department of Biological Chemistry and Pharmacology, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA
| | - Ian F Price
- Department of Biological Chemistry and Pharmacology, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA; Ohio State Biochemistry Program, Columbus, OH 43210, USA
| | - Wen Tang
- Department of Biological Chemistry and Pharmacology, Columbus, OH 43210, USA; Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
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50
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Yu Y, Ren KM, Chen XL. Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice. World J Diabetes 2021; 12:1116-1130. [PMID: 34326959 PMCID: PMC8311480 DOI: 10.4239/wjd.v12.i7.1116] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/11/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND As one of the major microvascular complications of diabetes, diabetic retinopathy (DR) is the leading cause of blindness in the working age population. Because the extremely complex pathogenesis of DR has not been fully clarified, the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization (RNV) has great harm to the visual acuity of patients.
AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA (piRNA) in proliferative DR mice and select piRNA related to RNV.
METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group (CG) and proliferative DR (PDR) group as experimental group (EG), with 50 mice in each group. Samples were collected from both groups at the same time, and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining. The retinal tissues were collected for second-generation high-throughput sequencing, and the differentially expressed piRNA between the CG and EG was detected, and polymerase chain reaction (PCR) was conducted for verification. The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes.
RESULTS In the CG there was no perfusion area, neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap. In the EG, there were a lot of nonperfused areas, new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina. There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups. High-throughput sequencing analysis showed that compared with the CG, a total of 79 piRNAs were differentially expressed in EG, among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated. Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation. Ten piRNAs were selected for PCR, and the results showed that the expression of piR-MMU-40373735, piR-MMU-61121420, piR-MMU-55687822, piR-MMU-1373887 were high, and the expression of piR-MMU-7401535, piR-MMU-4773779, piR-MMU-1304999, and piR-MMU-5160126 were low, which were consistent with the sequencing results.
CONCLUSION In the EG, the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation, suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.
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Affiliation(s)
- Yong Yu
- Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Kai-Ming Ren
- Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Xiao-Long Chen
- Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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