Regulation of Co-transcriptional Pre-mRNA Splicing by m6 A through the Low-Complexity Protein hnRNPG.

Journal Article (Journal Article)

N6 -methyladenosine (m6 A) modification occurs co-transcriptionally and impacts pre-mRNA processing; however, the mechanism of co-transcriptional m6 A-dependent alternative splicing regulation is still poorly understood. Heterogeneous nuclear ribonucleoprotein G (hnRNPG) is an m6 A reader protein that binds RNA through RRM and Arg-Gly-Gly (RGG) motifs. Here, we show that hnRNPG directly binds to the phosphorylated carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII) using RGG motifs in its low-complexity region. Through interactions with the phosphorylated CTD and nascent RNA, hnRNPG associates co-transcriptionally with RNAPII and regulates alternative splicing transcriptome-wide. m6 A near splice sites in nascent pre-mRNA modulates hnRNPG binding, which influences RNAPII occupancy patterns and promotes exon inclusion. Our results reveal an integrated mechanism of co-transcriptional m6 A-mediated splicing regulation, in which an m6 A reader protein uses RGG motifs to co-transcriptionally interact with both RNAPII and m6 A-modified nascent pre-mRNA to modulate RNAPII occupancy and alternative splicing.

Full Text

Duke Authors

Cited Authors

  • Zhou, KI; Shi, H; Lyu, R; Wylder, AC; Matuszek, Ż; Pan, JN; He, C; Parisien, M; Pan, T

Published Date

  • October 2019

Published In

Volume / Issue

  • 76 / 1

Start / End Page

  • 70 - 81.e9

PubMed ID

  • 31445886

Pubmed Central ID

  • PMC6778029

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2019.07.005

Language

  • eng