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A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA

RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions of POLR3G and POLR3GL to transcription potential has remained poorly defined. Here, we discover that loss of subunit P...

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Autores principales: Van Bortle, Kevin, Marciano, David P., Liu, Qing, Chou, Tristan, Lipchik, Andrew M., Gollapudi, Sanjay, Geller, Benjamin S., Monte, Emma, Kamakaka, Rohinton T., Snyder, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151912/
https://www.ncbi.nlm.nih.gov/pubmed/35637192
http://dx.doi.org/10.1038/s41467-022-30323-6
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author Van Bortle, Kevin
Marciano, David P.
Liu, Qing
Chou, Tristan
Lipchik, Andrew M.
Gollapudi, Sanjay
Geller, Benjamin S.
Monte, Emma
Kamakaka, Rohinton T.
Snyder, Michael P.
author_facet Van Bortle, Kevin
Marciano, David P.
Liu, Qing
Chou, Tristan
Lipchik, Andrew M.
Gollapudi, Sanjay
Geller, Benjamin S.
Monte, Emma
Kamakaka, Rohinton T.
Snyder, Michael P.
author_sort Van Bortle, Kevin
collection PubMed
description RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions of POLR3G and POLR3GL to transcription potential has remained poorly defined. Here, we discover that loss of subunit POLR3G is accompanied by a restricted repertoire of genes transcribed by Pol III. Particularly sensitive is snaR-A, a small noncoding RNA implicated in cancer proliferation and metastasis. Analysis of Pol III isoform biases and downstream chromatin features identifies loss of POLR3G and snaR-A during differentiation, and conversely, re-establishment of POLR3G gene expression and SNAR-A gene features in cancer contexts. Our results support a model in which Pol III identity functions as an important transcriptional regulatory mechanism. Upregulation of POLR3G, which is driven by MYC, identifies a subgroup of patients with unfavorable survival outcomes in specific cancers, further implicating the POLR3G-enhanced transcription repertoire as a potential disease factor.
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spelling pubmed-91519122022-06-01 A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA Van Bortle, Kevin Marciano, David P. Liu, Qing Chou, Tristan Lipchik, Andrew M. Gollapudi, Sanjay Geller, Benjamin S. Monte, Emma Kamakaka, Rohinton T. Snyder, Michael P. Nat Commun Article RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions of POLR3G and POLR3GL to transcription potential has remained poorly defined. Here, we discover that loss of subunit POLR3G is accompanied by a restricted repertoire of genes transcribed by Pol III. Particularly sensitive is snaR-A, a small noncoding RNA implicated in cancer proliferation and metastasis. Analysis of Pol III isoform biases and downstream chromatin features identifies loss of POLR3G and snaR-A during differentiation, and conversely, re-establishment of POLR3G gene expression and SNAR-A gene features in cancer contexts. Our results support a model in which Pol III identity functions as an important transcriptional regulatory mechanism. Upregulation of POLR3G, which is driven by MYC, identifies a subgroup of patients with unfavorable survival outcomes in specific cancers, further implicating the POLR3G-enhanced transcription repertoire as a potential disease factor. Nature Publishing Group UK 2022-05-30 /pmc/articles/PMC9151912/ /pubmed/35637192 http://dx.doi.org/10.1038/s41467-022-30323-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Van Bortle, Kevin
Marciano, David P.
Liu, Qing
Chou, Tristan
Lipchik, Andrew M.
Gollapudi, Sanjay
Geller, Benjamin S.
Monte, Emma
Kamakaka, Rohinton T.
Snyder, Michael P.
A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
title A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
title_full A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
title_fullStr A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
title_full_unstemmed A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
title_short A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA
title_sort cancer-associated rna polymerase iii identity drives robust transcription and expression of snar-a noncoding rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151912/
https://www.ncbi.nlm.nih.gov/pubmed/35637192
http://dx.doi.org/10.1038/s41467-022-30323-6
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