Efficient RNA polymerase II pause release requires U2 snRNP function.
Mol Cell
; 81(9): 1920-1934.e9, 2021 05 06.
Article
in En
| MEDLINE
| ID: mdl-33689748
ABSTRACT
Transcription by RNA polymerase II (Pol II) is coupled to pre-mRNA splicing, but the underlying mechanisms remain poorly understood. Co-transcriptional splicing requires assembly of a functional spliceosome on nascent pre-mRNA, but whether and how this influences Pol II transcription remains unclear. Here we show that inhibition of pre-mRNA branch site recognition by the spliceosome component U2 snRNP leads to a widespread and strong decrease in new RNA synthesis from human genes. Multiomics analysis reveals that inhibition of U2 snRNP function increases the duration of Pol II pausing in the promoter-proximal region, impairs recruitment of the pause release factor P-TEFb, and reduces Pol II elongation velocity at the beginning of genes. Our results indicate that efficient release of paused Pol II into active transcription elongation requires the formation of functional spliceosomes and that eukaryotic mRNA biogenesis relies on positive feedback from the splicing machinery to the transcription machinery.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA Polymerase II
/
RNA, Messenger
/
Spliceosomes
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Ribonucleoprotein, U2 Small Nuclear
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Transcription Elongation, Genetic
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Cell
Journal subject:
BIOLOGIA MOLECULAR
Year:
2021
Document type:
Article
Affiliation country: