Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Oct 17, 2023; 14(5): 84-98
Published online Oct 17, 2023. doi: 10.4331/wjbc.v14.i5.84
Protein arginine methyltransferase 6 is a novel substrate of protein arginine methyltransferase 1
Meng-Tong Cao, You Feng, Y George Zheng
Meng-Tong Cao, You Feng, Y George Zheng, Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, United States
Author contributions: Cao MT, Feng Y and Zheng YG designed the research study; Cao MT and Feng Y performed the experiments; All authors analyzed the data, wrote the manuscript, and have read and approve the final manuscript.
Supported by National Institutes of Health, No. 5R01GM126154 and No. 1R35GM149230.
Institutional review board statement: The study was reviewed and approved by the University of Georgia Institutional Biosafety Committee protocol number.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Y George Zheng, PhD, Professor, Department of Pharmaceutical and Biomedical Sciences, University of Georgia, No. 250 W. Green St., Athens, GA 30602, United States. yzheng@uga.edu
Received: July 19, 2023
Peer-review started: July 19, 2023
First decision: August 31, 2023
Revised: September 8, 2023
Accepted: September 26, 2023
Article in press: September 26, 2023
Published online: October 17, 2023
Processing time: 85 Days and 18 Hours
ARTICLE HIGHLIGHTS
Research background

Post-translational modifications play key roles in various biological processes. Protein arginine methyltransferases (PRMTs) transfer the methyl group to specific arginine residues. Both PRMT1 and PRMT6 have emerges as crucial factors in the development and progression of multiple cancer types. We posit that PRMT1 and PRMT6 might interplay directly or in-directly in multiple ways accounting for shared disease phenotypes.

Research motivation

The tumor-promoting roles of PRMT1 and PRMT6 in oncology are executed through their methylation of histone and non-histone substrates. Expression profile analysis suggests that PRMT1 and PRMT6 are both involved in multiple pathways which are fundamental for cell proliferation. We posit that PRMT1 and PRMT6 might interplay directly or in-directly for shared disease phenotypes. Thereby, neutralizing these enzymes’ activities or their interactions may interfere with tumor progression and lead to anticancer beneficial effects.

Research objectives

Understanding the role and function of PRMTs and how they interact with each other, identification of the methylation site (s) on PRMT6. Knowing the mechanism of this intercommunication will help develop inhibitor of tumor progression and increase cancer therapeutic effect. Knowing the interaction between PRMT1 and PRMT6 regulate the enzymatic activity of PRMT6.

Research methods

Gel electrophoresis autoradiography was performed to test the methyltranferase activity of PRMTs and characterize the kinetics parameters of PRMTs. Liquid chromatography-tandem mass spectrometry analysis was performed to detect the PRMT6 methylation sites.

Research results

In this study we investigated the interaction between PRMT1 and PRMT6, and PRMT6 was shown to be a novel substrate of PRMT1. We identified specific arginine residues of PRMT6 that are methylated by PRMT1, with R106 being the major methylation site. Combined biochemical and cellular data showed that PRMT1 downregulates the enzymatic activity of PRMT6 in histone H3 methylation.

Research conclusions

PRMT6 is methylated by PRMT1 and R106 is a major methylation site induced by PRMT1. PRMT1 methylation suppresses the activity of PRMT6.

Research perspectives

Future research is warranted to elucidate whether and how various signaling pathways regulated by PRMT6 can be counteracted by PRMT1. Priority should be given on the examination of functional consequences of PRMT6 methylation mediated by PRMT1 on different protein substrates and in different biological contexts.