1. Efficient RNA polymerase II pause release requires U2 snRNP function.
- Author
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Caizzi L, Monteiro-Martins S, Schwalb B, Lysakovskaia K, Schmitzova J, Sawicka A, Chen Y, Lidschreiber M, and Cramer P
- Subjects
- Animals, Drosophila Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster enzymology, Drosophila melanogaster genetics, Feedback, Physiological, Gene Expression Regulation, HeLa Cells, Humans, K562 Cells, Positive Transcriptional Elongation Factor B genetics, Positive Transcriptional Elongation Factor B metabolism, Promoter Regions, Genetic, RNA Polymerase II genetics, RNA Precursors genetics, RNA Precursors metabolism, RNA Splicing, RNA, Messenger genetics, Ribonucleoprotein, U2 Small Nuclear genetics, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Spliceosomes genetics, Time Factors, RNA Polymerase II metabolism, RNA, Messenger biosynthesis, Ribonucleoprotein, U2 Small Nuclear metabolism, Spliceosomes enzymology, Transcription Elongation, Genetic
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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