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| Status |
Public on Oct 28, 2022 |
| Title |
Integrator endonuclease drives promoter-proximal termination at all RNAPII transcribed loci (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Pausing of RNA polymerase II (RNAPII) in early elongation is critical for gene regulation. Paused RNAPII can be released into productive elongation by the kinase P-TEFb or targeted for premature termination by the Integrator complex. Integrator comprises endonuclease and phosphatase activities, driving termination through cleavage of nascent RNA and removal of stimulatory phosphorylation. To probe the direct consequences of Integrator activity, we generated a degron system to rapidly deplete the Integrator endonuclease INTS11. Degradation of INTS11 elicits a nearly universal increase in RNAPII escape from promoter regions. However, these RNAPII complexes fail to achieve optimal elongation rates and reveal continued Integrator phosphatase activity. Short transcripts are thus selectively upregulated by INTS11 loss, including many non-coding RNAs, transcription factors and signaling regulators. Together, our data indicate a common function for INTS11 at all RNAPII loci, with differential effects on particular genes, pathways or RNA biotypes reflecting transcript lengths rather than Integrator specificity.
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| Overall design |
Examination of 6 samples by RNA-seq (3 biological replicate sets of F121-9 cells: control knockdown; INTS11 knockdown); also 2 biological replicate sets of untreated F121-9 cells
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| Contributor(s) |
Adelman K, Wagner EJ, Stein CB, Field AR, Mimoso CA, Zhao C, Huang K |
| Citation(s) |
36309014 |
| |
| Submission date |
Apr 12, 2022 |
| Last update date |
Jan 27, 2023 |
| Contact name |
Karen Adelman |
| E-mail(s) |
karen_adelman@hms.harvard.edu
|
| Organization name |
Harvard Medical School
|
| Department |
Biological Chemistry and Molecular Pharmacology
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| Street address |
45 Shattuck St. LHRRB-201a
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE200702 |
Integrator endonuclease drives promoter-proximal termination at all RNAPII transcribed loci |
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| Relations |
| BioProject |
PRJNA826102 |
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