Arginine methylation expands the regulatory mechanisms and extends the genomic landscape under E2F control

E2F is a family of master transcription regulators involved in mediating diverse cell fates. Here, we show that residue-specific arginine methylation (meR) by PRMT5 enables E2F1 to regulate many genes at the level of alternative RNA splicing, rather than through its classical transcription-based mec...

Full description

Saved in:
Bibliographic Details
Published in:Science advances 2019-06, Vol.5 (6), p.eaaw4640-eaaw4640
Main Authors: Roworth, Alice Poppy, Carr, Simon Mark, Liu, Geng, Barczak, Wojciech, Miller, Rebecca Louise, Munro, Shonagh, Kanapin, Alexander, Samsonova, Anastasia, La Thangue, Nicholas B
Format: Article
Language:English
Subjects:
Alternative Splicing - genetics
Arginine - genetics
Cancer
Cell Biology
Cell Line
Chromatin - genetics
E2F Transcription Factors - genetics
Endopeptidases - genetics
Genomics
Humans
Methylation
RNA - genetics
SciAdv r-articles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:E2F is a family of master transcription regulators involved in mediating diverse cell fates. Here, we show that residue-specific arginine methylation (meR) by PRMT5 enables E2F1 to regulate many genes at the level of alternative RNA splicing, rather than through its classical transcription-based mechanism. The p100/TSN tudor domain protein reads the meR mark on chromatin-bound E2F1, allowing snRNA components of the splicing machinery to assemble with E2F1. A large set of RNAs including spliced variants associate with E2F1 by virtue of the methyl mark. By focusing on the deSUMOylase SENP7 gene, which we identified as an E2F target gene, we establish that alternative splicing is functionally important for E2F1 activity. Our results reveal an unexpected consequence of arginine methylation, where reader-writer interplay widens the mechanism of control by E2F1, from transcription factor to regulator of alternative RNA splicing, thereby extending the genomic landscape under E2F1 control.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aaw4640