A combinatorial approach to uncover an additional Integrator subunit
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
RNA polymerase II (RNAPII) controls expression of all protein-coding genes and most noncoding loci in higher eukaryotes. Calibrating RNAPII activity requires an assortment of polymerase-associated factors that are recruited at sites of active transcription. The Integrator complex is one of the most elusive transcriptional regulators in metazoans, deemed to be recruited after initiation to help establish and modulate paused RNAPII. Integrator is known to be composed of 14 subunits that assemble and operate in a modular fashion. We employed proteomics and machine-learning structure prediction (AlphaFold2) to identify an additional Integrator subunit, INTS15. We report that INTS15 assembles primarily with the INTS13/14/10 module and interfaces with the Int-PP2A module. Functional genomics analysis further reveals a role for INTS15 in modulating RNAPII pausing at a subset of genes. Our study shows that omics approaches combined with AlphaFold2-based predictions provide additional insights into the molecular architecture of large and dynamic multiprotein complexes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 3 vom: 28. März, Seite 112244 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Offley, Sarah R [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2023 Date Revised 04.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112244 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a RNA polymerase II (RNAPII) controls expression of all protein-coding genes and most noncoding loci in higher eukaryotes. Calibrating RNAPII activity requires an assortment of polymerase-associated factors that are recruited at sites of active transcription. The Integrator complex is one of the most elusive transcriptional regulators in metazoans, deemed to be recruited after initiation to help establish and modulate paused RNAPII. Integrator is known to be composed of 14 subunits that assemble and operate in a modular fashion. We employed proteomics and machine-learning structure prediction (AlphaFold2) to identify an additional Integrator subunit, INTS15. We report that INTS15 assembles primarily with the INTS13/14/10 module and interfaces with the Int-PP2A module. Functional genomics analysis further reveals a role for INTS15 in modulating RNAPII pausing at a subset of genes. Our study shows that omics approaches combined with AlphaFold2-based predictions provide additional insights into the molecular architecture of large and dynamic multiprotein complexes | ||
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a CP: Neuroscience | |
| 650 | 4 | |a Integrator complex | |
| 650 | 4 | |a RNA polymerase II | |
| 650 | 4 | |a RNA polymerase II pausing | |
| 650 | 4 | |a large protein complexes | |
| 650 | 4 | |a molecular modeling | |
| 650 | 4 | |a omics | |
| 650 | 4 | |a pause-release | |
| 650 | 4 | |a transcription | |
| 650 | 4 | |a transcription factors | |
| 650 | 4 | |a transcriptional regulation | |
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| 700 | 1 | |a Zucco, Avery |e verfasserin |4 aut | |
| 700 | 1 | |a Fraudeau, Angelique |e verfasserin |4 aut | |
| 700 | 1 | |a Welsh, Sarah A |e verfasserin |4 aut | |
| 700 | 1 | |a Razew, Michal |e verfasserin |4 aut | |
| 700 | 1 | |a Galej, Wojciech P |e verfasserin |4 aut | |
| 700 | 1 | |a Gardini, Alessandro |e verfasserin |4 aut | |
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