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  Efficient RNA polymerase II pause release requires U2 snRNP function

Caizzi, L., Monteiro-Martins, S., Schwalb, B., Lysakovskaya, K., Schmitzova, J., Sawicka, A., et al. (2021). Efficient RNA polymerase II pause release requires U2 snRNP function. Molecular Cell, 81(9), 1920-1934.e9. doi:10.1016/j.molcel.2021.02.016.

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 Creators:
Caizzi, L.1, Author              
Monteiro-Martins, S., Author
Schwalb, B.1, Author              
Lysakovskaya, K., Author
Schmitzova, J., Author
Sawicka, A.1, Author              
Chen, Y.1, Author              
Lidschreiber, M.1, Author              
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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Free keywords: transcription; splicing; co-transcriptional pre-mRNA splicing; RNA polymerase II; SF3B; U2 snRNP; pladienolide B; spliceostatin A; U2 AMO; transcription elongation
 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.

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Language(s): eng - English
 Dates: 2021-03-082021-05-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2021.02.016
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Pages: - Volume / Issue: 81 (9) Sequence Number: - Start / End Page: 1920 - 1934.e9 Identifier: -