RBM22 Regulates RNA Polymerase II 5' Pausing, Elongation Rate, and Termination by Coordinating 7SK-P-TEFb Complex and SPT5

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2024 Apr 19

PMID 38641822

Authors

Xian Du

Wenying Qin

Chunyu Yang

Lin Dai

Mingkui San

Yingdan Xia

Siyu Zhou

Mengyang Wang

Shuang Wu

Shaorui Zhang

Huiting Zhou

Fangshu Li

Fang He

Jingfeng Tang

Jia-Yu Chen

Yu Zhou

Rui Xiao

Affiliations

Soon will be listed here.

Abstract

Background: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood.

Results: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level.

Conclusions: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

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