RBM22 regulates RNA polymerase II 5′ pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5

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. Here, we describe a direct role of splicing factor RBM22 in c...

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Published inGenome Biology Vol. 25; no. 1; p. 102
Main Authors Du, Xian, Qin, Wenying, Yang, Chunyu, Dai, Lin, San, Mingkui, Xia, Yingdan, Zhou, Siyu, Wang, Mengyang, Wu, Shuang, Zhang, Shaorui, Zhou, Huiting, Li, Fangshu, He, Fang, Tang, Jingfeng, Chen, Jia-Yu, Zhou, Yu, Xiao, Rui
Format Journal Article
LanguageEnglish
Published England BioMed Central 19.04.2024
BMC
Subjects
5′ pausing
Chromatin
DNA-directed RNA polymerase
Elongation
Gene expression
genes
Genomes
Homeostasis
Humans
loci
Molecular modelling
Positive Transcriptional Elongation Factor B - genetics
Positive Transcriptional Elongation Factor B - metabolism
Proteins
RBM22
RNA
RNA polymerase
RNA polymerase II
RNA Polymerase II - metabolism
RNA Splicing
RNA Splicing Factors - genetics
Splicing factors
transcription (genetics)
Transcription elongation
Transcription termination
Transcription, Genetic
Transcriptional Elongation Factors - genetics
Transcriptional Elongation Factors - metabolism
Transcription termination
Transcription elongation
5′ pausing
RNA polymerase II
RBM22
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Abstract 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. 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. 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.
AbstractList 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. 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. 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.
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.
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.BACKGROUNDSplicing 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.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.RESULTSHere, 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.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.CONCLUSIONSOur 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.
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.
BackgroundSplicing 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.ResultsHere, 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.ConclusionsOur 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.
ArticleNumber 102
Author Zhou, Huiting
Zhou, Siyu
Dai, Lin
Wu, Shuang
Zhou, Yu
Zhang, Shaorui
He, Fang
Qin, Wenying
Du, Xian
Tang, Jingfeng
Yang, Chunyu
Xiao, Rui
San, Mingkui
Xia, Yingdan
Chen, Jia-Yu
Wang, Mengyang
Li, Fangshu
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crossref_primary_10_1186_s13046_025_03347_1
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Keywords Transcription termination
Transcription elongation
5′ pausing
RNA polymerase II
RBM22
Language English
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  doi: 10.1128/MCB.01117-15
– volume: 30
  start-page: 923
  year: 2014
  ident: 3242_CR111
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btt656
SSID ssj0019426
ssj0017866
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Snippet Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular...
BackgroundSplicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying...
BACKGROUND : Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying...
Abstract Background Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The...
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StartPage 102
SubjectTerms 5′ pausing
Chromatin
DNA-directed RNA polymerase
Elongation
Gene expression
genes
Genomes
Homeostasis
Humans
loci
Molecular modelling
Positive Transcriptional Elongation Factor B - genetics
Positive Transcriptional Elongation Factor B - metabolism
Proteins
RBM22
RNA
RNA polymerase
RNA polymerase II
RNA Polymerase II - metabolism
RNA Splicing
RNA Splicing Factors - genetics
Splicing factors
transcription (genetics)
Transcription elongation
Transcription termination
Transcription, Genetic
Transcriptional Elongation Factors - genetics
Transcriptional Elongation Factors - metabolism
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Title RBM22 regulates RNA polymerase II 5′ pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5
URI https://www.ncbi.nlm.nih.gov/pubmed/38641822
https://www.proquest.com/docview/3054212001
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https://www.proquest.com/docview/3153715270
https://doaj.org/article/75c3899345da4456a07654ed5537c011
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