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PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex
RNA polymerase elongation along the gene body is tightly regulated to ensure proper transcription and alternative splicing events. Understanding the mechanism and factors critical in regulating the rate of RNA polymerase II elongation and processivity is clearly important. Recently we showed that PA...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600911/ https://www.ncbi.nlm.nih.gov/pubmed/36291070 http://dx.doi.org/10.3390/cells11203202 |
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author | Matveeva, Elena A. Dhahri, Hejer Fondufe-Mittendorf, Yvonne |
author_facet | Matveeva, Elena A. Dhahri, Hejer Fondufe-Mittendorf, Yvonne |
author_sort | Matveeva, Elena A. |
collection | PubMed |
description | RNA polymerase elongation along the gene body is tightly regulated to ensure proper transcription and alternative splicing events. Understanding the mechanism and factors critical in regulating the rate of RNA polymerase II elongation and processivity is clearly important. Recently we showed that PARP1, a well-known DNA repair protein, when bound to chromatin, regulates RNA polymerase II elongation. However, the mechanism by which it does so is not known. In the current study, we aimed to tease out how PARP1 regulates RNAPII elongation. We show, both in vivo and in vitro, that PARP1 binds directly to the Integrator subunit 3 (IntS3), a member of the elongation Integrator complex. The association between the two proteins is mediated via the C-terminal domain of PARP1 to the C-terminal domain of IntS3. Interestingly, the occupancy of IntS3 along two PARP1 target genes mimicked that of PARP1, suggesting a role in its recruitment/assembly of elongation factors. Indeed, the knockdown of PARP1 resulted in differential chromatin association and gene occupancy of IntS3 and other key elongation factors. Most of these PARP1-mediated effects were due to the physical presence of PARP1 rather than its PARylation activity. These studies argue that PARP1 controls the progressive RNAPII elongation complexes. In summary, we present a platform to begin to decipher PARP1′s role in recruiting/scaffolding elongation factors along the gene body regions during RNA polymerase II elongation and gene regulation. |
format | Online Article Text |
id | pubmed-9600911 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96009112022-10-27 PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex Matveeva, Elena A. Dhahri, Hejer Fondufe-Mittendorf, Yvonne Cells Article RNA polymerase elongation along the gene body is tightly regulated to ensure proper transcription and alternative splicing events. Understanding the mechanism and factors critical in regulating the rate of RNA polymerase II elongation and processivity is clearly important. Recently we showed that PARP1, a well-known DNA repair protein, when bound to chromatin, regulates RNA polymerase II elongation. However, the mechanism by which it does so is not known. In the current study, we aimed to tease out how PARP1 regulates RNAPII elongation. We show, both in vivo and in vitro, that PARP1 binds directly to the Integrator subunit 3 (IntS3), a member of the elongation Integrator complex. The association between the two proteins is mediated via the C-terminal domain of PARP1 to the C-terminal domain of IntS3. Interestingly, the occupancy of IntS3 along two PARP1 target genes mimicked that of PARP1, suggesting a role in its recruitment/assembly of elongation factors. Indeed, the knockdown of PARP1 resulted in differential chromatin association and gene occupancy of IntS3 and other key elongation factors. Most of these PARP1-mediated effects were due to the physical presence of PARP1 rather than its PARylation activity. These studies argue that PARP1 controls the progressive RNAPII elongation complexes. In summary, we present a platform to begin to decipher PARP1′s role in recruiting/scaffolding elongation factors along the gene body regions during RNA polymerase II elongation and gene regulation. MDPI 2022-10-12 /pmc/articles/PMC9600911/ /pubmed/36291070 http://dx.doi.org/10.3390/cells11203202 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matveeva, Elena A. Dhahri, Hejer Fondufe-Mittendorf, Yvonne PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex |
title | PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex |
title_full | PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex |
title_fullStr | PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex |
title_full_unstemmed | PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex |
title_short | PARP1′s Involvement in RNA Polymerase II Elongation: Pausing and Releasing Regulation through the Integrator and Super Elongation Complex |
title_sort | parp1′s involvement in rna polymerase ii elongation: pausing and releasing regulation through the integrator and super elongation complex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600911/ https://www.ncbi.nlm.nih.gov/pubmed/36291070 http://dx.doi.org/10.3390/cells11203202 |
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