Regulation of Co-transcriptional Pre-mRNA Splicing by m⁶A through the Low-Complexity Protein hnRNPG.

ABSTRACT: N⁶-methyladenosine (m⁶A) modification occurs co-transcriptionally and impacts pre-mRNA processing; however, the mechanism of co-transcriptional m⁶A-dependent alternative splicing regulation is still poorly understood. Heterogeneous nuclear ribonucleoprotein G (hnRNPG) is an m⁶A 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. m⁶A near splice sites in nascent pre-mRNA modulates

SUBMITTER: Zhou KI 

PROVIDER: S-EPMC6778029 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature