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
Abstract
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.

AIM

To investigate the mechanism of the interaction between PRMT1 and PRMT6.

METHODS

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

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.

CONCLUSION

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

Keywords: Posttranslational modification, Arginine methylation, Protein arginine methyltransferase 1, Protein arginine methyltransferase 6, Cross-talk, Protein-protein interaction

Core Tip: We reported the interplay between protein arginine methyltransferase (PRMT) 1 and PRMT6, and PRMT6 is a substrate of PRMT1. The major methylation site in PRMT6 is R106 for PRMT1 catalysis and the methylation by PRMT1 regulates the enzymatic activity of PRMT6. This study is important for understanding the cross-talking relationship between PRMTs.