RT Journal Article
SR Electronic
T1 Arginine methylation expands the regulatory mechanisms and extends the genomic landscape under E2F control
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaaw4640
DO 10.1126/sciadv.aaw4640
VO 5
IS 6
A1 Roworth, Alice Poppy
A1 Carr, Simon Mark
A1 Liu, Geng
A1 Barczak, Wojciech
A1 Miller, Rebecca Louise
A1 Munro, Shonagh
A1 Kanapin, Alexander
A1 Samsonova, Anastasia
A1 La Thangue, Nicholas B.
YR 2019
UL http://advances.sciencemag.org/content/5/6/eaaw4640.abstract
AB 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.