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| Status |
Public on Mar 30, 2021 |
| Title |
The 7SK/P-TEFb snRNP controls ultraviolet radiation-induced transcriptional reprogramming |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Releasing promoter-proximally-paused RNA polymerase II (RNAPII) by the positive transcription elongation factor b (P-TEFb) is a central regulatory step of eukaryotic mRNA synthesis. The nuclear activity of P-TEFb is controlled mainly by the 7SK small nuclear RNP (snRNP) which sequesters active P-TEFb into inactive 7SK/P-TEFb snRNP. Here we demonstrate that under normal culture conditions, the lack of 7SK snRNP has only a minor impact on global RNAPII transcription and promoter-proximal pausing without detectable consequences on cell growth and proliferation. However, upon ultraviolet (UV) light-induced DNA damage, cells lacking 7SK have a defective transcriptional response and highly reduced viability. Both UV-induced release of ‘lesion-scanning’ polymerases and activation of key early responsive genes are compromised in the absence of 7SK. We show that proper induction of 7SK-dependent UV-responsive genes, namely efficient release of paused RNAPII and recruitment of key elongation factors, requires P-TEFb activity directly mobilized from the nucleoplasmic 7SK/P-TEFb snRNP.
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| Overall design |
ChIRP-seq of 7SK in HAP1 and HAP1-7SK-KO cells -/+ 1h UV, mNET-seq of total pol II in HAP1 and HAP1-7SK-KO cells -/+ 1h, 2h, or 4h UV.
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| Contributor(s) |
Studniarek C, Tellier M, Martin P, Murphy S, Kiss T, Egloff S |
| Citation(s) |
33852864 |
| |
| Submission date |
Mar 16, 2020 |
| Last update date |
Jun 29, 2021 |
| Contact name |
Michael Tellier |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Leicester
|
| Department |
Department of Molecular and Cell Biology
|
| Lab |
Tellier Lab
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| Street address |
Lancaster Road
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| City |
Leicester |
| State/province |
Select State |
| ZIP/Postal code |
LE1 7HB |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA612855 |
| SRA |
SRP252981 |
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