Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Type I PRMTs and PRMT5 Independently Regulate Both snRNP Arginine Methylation and Post-Transcriptional Splicing

View ORCID ProfileMaxim I. Maron, View ORCID ProfileEmmanuel S. Burgos, Varun Gupta, Alyssa D. Casill, Brian Kosmyna, Hongshan Chen, View ORCID ProfileMatthew J. Gamble, View ORCID ProfileCharles C. Query, View ORCID ProfileDavid Shechter
doi: https://doi.org/10.1101/2020.11.18.389288
Maxim I. Maron
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maxim I. Maron
Emmanuel S. Burgos
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Emmanuel S. Burgos
Varun Gupta
2Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alyssa D. Casill
3Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian Kosmyna
2Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongshan Chen
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
4Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China, 211166
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew J. Gamble
3Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Matthew J. Gamble
Charles C. Query
2Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Charles C. Query
David Shechter
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David Shechter
  • For correspondence: david.shechter@einsteinmed.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Protein arginine methyltransferases (PRMTs) methylate histones, splicing factors, and many other nuclear proteins. Type I enzymes (PRMT1-4,6,8) catalyze mono- (Rme1/MMA) and asymmetric (Rme2a/ADMA) dimethylation; Type II enzymes (PRMT5,9) catalyze mono- and symmetric (Rme2s/SDMA) dimethylation. Misregulation of PRMTs in multiple types of cancers is associated with aberrant gene expression and RNA splicing. To understand the specific mechanisms of PRMT activity in splicing regulation, we treated cells with the PRMT5 inhibitor GSK591 and the Type I inhibitor MS023 and probed their transcriptomic consequences. We discovered that Type I PRMTs and PRMT5 inversely regulate core spliceosomal Sm protein Rme2s and intron retention. Loss of Sm Rme2s is associated with the accumulation of polyadenylated RNA containing retained introns and snRNPs on chromatin. Conversely, increased Sm Rme2s correlates with decreased intron retention and chromatin-association of intron-containing polyadenylated RNA. Using the newly developed SKaTER-seq model, comprehensive and quantitative analysis of co-transcriptional splicing revealed that either Type I PRMT or PRMT5 inhibition resulted in slower splicing rates. Surprisingly, altered co-transcriptional splicing kinetics correlated poorly with ultimate changes in alternatively spliced mRNA. Quantitation of retained intron decay following inhibition of nascent transcription revealed that Type I PRMTs and PRMT5 reciprocally regulate post-transcriptional splicing efficiency.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted November 19, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Type I PRMTs and PRMT5 Independently Regulate Both snRNP Arginine Methylation and Post-Transcriptional Splicing
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Type I PRMTs and PRMT5 Independently Regulate Both snRNP Arginine Methylation and Post-Transcriptional Splicing
Maxim I. Maron, Emmanuel S. Burgos, Varun Gupta, Alyssa D. Casill, Brian Kosmyna, Hongshan Chen, Matthew J. Gamble, Charles C. Query, David Shechter
bioRxiv 2020.11.18.389288; doi: https://doi.org/10.1101/2020.11.18.389288
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Type I PRMTs and PRMT5 Independently Regulate Both snRNP Arginine Methylation and Post-Transcriptional Splicing
Maxim I. Maron, Emmanuel S. Burgos, Varun Gupta, Alyssa D. Casill, Brian Kosmyna, Hongshan Chen, Matthew J. Gamble, Charles C. Query, David Shechter
bioRxiv 2020.11.18.389288; doi: https://doi.org/10.1101/2020.11.18.389288

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4114)
  • Biochemistry (8816)
  • Bioengineering (6519)
  • Bioinformatics (23465)
  • Biophysics (11792)
  • Cancer Biology (9211)
  • Cell Biology (13325)
  • Clinical Trials (138)
  • Developmental Biology (7439)
  • Ecology (11413)
  • Epidemiology (2066)
  • Evolutionary Biology (15155)
  • Genetics (10439)
  • Genomics (14045)
  • Immunology (9173)
  • Microbiology (22159)
  • Molecular Biology (8813)
  • Neuroscience (47577)
  • Paleontology (350)
  • Pathology (1429)
  • Pharmacology and Toxicology (2492)
  • Physiology (3731)
  • Plant Biology (8082)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6039)
  • Zoology (1253)