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Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage

Coilin is a nuclear phosphoprotein that concentrates within Cajal bodies (CBs) and impacts small nuclear ribonucleoprotein (snRNP) biogenesis. Cisplatin and γ-irradiation, which cause distinct types of DNA damage, both trigger the nucleolar accumulation of coilin, and this temporally coincides with...

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Autores principales: Gilder, Andrew S., Do, Phi M., Carrero, Zunamys I, Cosman, Angela M., Broome, Hanna J., Velma, Venkatramreddy, Martinez, Luis A., Hebert, Michael D.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069010/
https://www.ncbi.nlm.nih.gov/pubmed/21289084
http://dx.doi.org/10.1091/mbc.E10-08-0731
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author Gilder, Andrew S.
Do, Phi M.
Carrero, Zunamys I
Cosman, Angela M.
Broome, Hanna J.
Velma, Venkatramreddy
Martinez, Luis A.
Hebert, Michael D.
author_facet Gilder, Andrew S.
Do, Phi M.
Carrero, Zunamys I
Cosman, Angela M.
Broome, Hanna J.
Velma, Venkatramreddy
Martinez, Luis A.
Hebert, Michael D.
author_sort Gilder, Andrew S.
collection PubMed
description Coilin is a nuclear phosphoprotein that concentrates within Cajal bodies (CBs) and impacts small nuclear ribonucleoprotein (snRNP) biogenesis. Cisplatin and γ-irradiation, which cause distinct types of DNA damage, both trigger the nucleolar accumulation of coilin, and this temporally coincides with the repression of RNA polymerase I (Pol I) activity. Knockdown of endogenous coilin partially overrides the Pol I transcriptional arrest caused by cisplatin, while both ectopically expressed and exogenous coilin accumulate in the nucleolus and suppress rRNA synthesis. In support of this mechanism, we demonstrate that both cisplatin and γ-irradiation induce the colocalization of coilin with RPA-194 (the largest subunit of Pol I), and we further show that coilin can specifically interact with RPA-194 and the key regulator of Pol I activity, upstream binding factor (UBF). Using chromatin immunoprecipitation analysis, we provide evidence that coilin modulates the association of Pol I with ribosomal DNA. Collectively, our data suggest that coilin acts to repress Pol I activity in response to cisplatin-induced DNA damage. Our findings identify a novel and unexpected function for coilin, independent of its role in snRNP biogenesis, establishing a new link between the DNA damage response and the inhibition of rRNA synthesis.
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spelling pubmed-30690102011-06-16 Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage Gilder, Andrew S. Do, Phi M. Carrero, Zunamys I Cosman, Angela M. Broome, Hanna J. Velma, Venkatramreddy Martinez, Luis A. Hebert, Michael D. Mol Biol Cell Articles Coilin is a nuclear phosphoprotein that concentrates within Cajal bodies (CBs) and impacts small nuclear ribonucleoprotein (snRNP) biogenesis. Cisplatin and γ-irradiation, which cause distinct types of DNA damage, both trigger the nucleolar accumulation of coilin, and this temporally coincides with the repression of RNA polymerase I (Pol I) activity. Knockdown of endogenous coilin partially overrides the Pol I transcriptional arrest caused by cisplatin, while both ectopically expressed and exogenous coilin accumulate in the nucleolus and suppress rRNA synthesis. In support of this mechanism, we demonstrate that both cisplatin and γ-irradiation induce the colocalization of coilin with RPA-194 (the largest subunit of Pol I), and we further show that coilin can specifically interact with RPA-194 and the key regulator of Pol I activity, upstream binding factor (UBF). Using chromatin immunoprecipitation analysis, we provide evidence that coilin modulates the association of Pol I with ribosomal DNA. Collectively, our data suggest that coilin acts to repress Pol I activity in response to cisplatin-induced DNA damage. Our findings identify a novel and unexpected function for coilin, independent of its role in snRNP biogenesis, establishing a new link between the DNA damage response and the inhibition of rRNA synthesis. The American Society for Cell Biology 2011-04-01 /pmc/articles/PMC3069010/ /pubmed/21289084 http://dx.doi.org/10.1091/mbc.E10-08-0731 Text en © 2011 Gilder et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Gilder, Andrew S.
Do, Phi M.
Carrero, Zunamys I
Cosman, Angela M.
Broome, Hanna J.
Velma, Venkatramreddy
Martinez, Luis A.
Hebert, Michael D.
Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage
title Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage
title_full Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage
title_fullStr Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage
title_full_unstemmed Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage
title_short Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage
title_sort coilin participates in the suppression of rna polymerase i in response to cisplatin-induced dna damage
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069010/
https://www.ncbi.nlm.nih.gov/pubmed/21289084
http://dx.doi.org/10.1091/mbc.E10-08-0731
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