|
| Status |
Public on Jan 31, 2021 |
| Title |
Efficient RNA polymerase II pause release requires U2 snRNP function |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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 in human cells. Multiomics analysis reveals that U2 snRNP inhibition 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 in the beginning of genes. Our results indicate that efficient release of paused Pol II into active transcription elongation requires 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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| |
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| Overall design |
Effect of U2 snRNP inhibition on transcription
|
| |
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| Contributor(s) |
Caizzi L, Monteiro-Martins S, Schwalb B, Lysakovskaia K, Schmitzova J, Sawicka A, Chen Y, Lidschreiber M, Cramer P |
| Citation(s) |
33689748 |
| |
| Submission date |
Apr 09, 2020 |
| Last update date |
May 03, 2021 |
| Contact name |
Sara Patricia Monteiro Martins |
| E-mail(s) |
[email protected]
|
| Organization name |
MPI for biophysical chemistry
|
| Department |
Molecular Biology
|
| Lab |
Cramer
|
| Street address |
Fassberg 11
|
| City |
Göttingen |
| ZIP/Postal code |
37077 |
| Country |
Germany |
| |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL21697 |
NextSeq 550 (Homo sapiens) |
|
| Samples (48)
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|
| Relations |
| BioProject |
PRJNA624181 |
| SRA |
SRP255915 |
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