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Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs
Cell cycle progression requires control of the abundance of several proteins and RNAs over space and time to properly transit from one phase to the next and to ensure faithful genomic inheritance in daughter cells. The proteasome, the main protein degradation system of the cell, facilitates the esta...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299679/ https://www.ncbi.nlm.nih.gov/pubmed/34739170 http://dx.doi.org/10.1111/febs.16261 |
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author | Cáceres‐Gutiérrez, Rodrigo E. Andonegui, Marco A. Oliva‐Rico, Diego A. González‐Barrios, Rodrigo Luna, Fernando Arriaga‐Canon, Cristian López‐Saavedra, Alejandro Prada, Diddier Castro, Clementina Parmentier, Laurent Díaz‐Chávez, José Alfaro‐Mora, Yair Navarro‐Delgado, Erick I. Fabian‐Morales, Eunice Tran, Bao Shetty, Jyoti Zhao, Yongmei Alcaraz, Nicolas De la Rosa, Carlos Reyes, José L. Hédouin, Sabrine Hubé, Florent Francastel, Claire Herrera, Luis A. |
author_facet | Cáceres‐Gutiérrez, Rodrigo E. Andonegui, Marco A. Oliva‐Rico, Diego A. González‐Barrios, Rodrigo Luna, Fernando Arriaga‐Canon, Cristian López‐Saavedra, Alejandro Prada, Diddier Castro, Clementina Parmentier, Laurent Díaz‐Chávez, José Alfaro‐Mora, Yair Navarro‐Delgado, Erick I. Fabian‐Morales, Eunice Tran, Bao Shetty, Jyoti Zhao, Yongmei Alcaraz, Nicolas De la Rosa, Carlos Reyes, José L. Hédouin, Sabrine Hubé, Florent Francastel, Claire Herrera, Luis A. |
author_sort | Cáceres‐Gutiérrez, Rodrigo E. |
collection | PubMed |
description | Cell cycle progression requires control of the abundance of several proteins and RNAs over space and time to properly transit from one phase to the next and to ensure faithful genomic inheritance in daughter cells. The proteasome, the main protein degradation system of the cell, facilitates the establishment of a proteome specific to each phase of the cell cycle. Its activity also strongly influences transcription. Here, we detected the upregulation of repetitive RNAs upon proteasome inhibition in human cancer cells using RNA‐seq. The effect of proteasome inhibition on centromeres was remarkable, especially on α‐Satellite RNAs. We showed that α‐Satellite RNAs fluctuate along the cell cycle and interact with members of the cohesin ring, suggesting that these transcripts may take part in the regulation of mitotic progression. Next, we forced exogenous overexpression and used gapmer oligonucleotide targeting to demonstrate that α‐Sat RNAs have regulatory roles in mitosis. Finally, we explored the transcriptional regulation of α‐Satellite DNA. Through in silico analyses, we detected the presence of CCAAT transcription factor‐binding motifs within α‐Satellite centromeric arrays. Using high‐resolution three‐dimensional immuno‐FISH and ChIP‐qPCR, we showed an association between the α‐Satellite upregulation and the recruitment of the transcription factor NFY‐A to the centromere upon MG132‐induced proteasome inhibition. Together, our results show that the proteasome controls α‐Satellite RNAs associated with the regulation of mitosis. |
format | Online Article Text |
id | pubmed-9299679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92996792022-07-21 Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs Cáceres‐Gutiérrez, Rodrigo E. Andonegui, Marco A. Oliva‐Rico, Diego A. González‐Barrios, Rodrigo Luna, Fernando Arriaga‐Canon, Cristian López‐Saavedra, Alejandro Prada, Diddier Castro, Clementina Parmentier, Laurent Díaz‐Chávez, José Alfaro‐Mora, Yair Navarro‐Delgado, Erick I. Fabian‐Morales, Eunice Tran, Bao Shetty, Jyoti Zhao, Yongmei Alcaraz, Nicolas De la Rosa, Carlos Reyes, José L. Hédouin, Sabrine Hubé, Florent Francastel, Claire Herrera, Luis A. FEBS J Original Articles Cell cycle progression requires control of the abundance of several proteins and RNAs over space and time to properly transit from one phase to the next and to ensure faithful genomic inheritance in daughter cells. The proteasome, the main protein degradation system of the cell, facilitates the establishment of a proteome specific to each phase of the cell cycle. Its activity also strongly influences transcription. Here, we detected the upregulation of repetitive RNAs upon proteasome inhibition in human cancer cells using RNA‐seq. The effect of proteasome inhibition on centromeres was remarkable, especially on α‐Satellite RNAs. We showed that α‐Satellite RNAs fluctuate along the cell cycle and interact with members of the cohesin ring, suggesting that these transcripts may take part in the regulation of mitotic progression. Next, we forced exogenous overexpression and used gapmer oligonucleotide targeting to demonstrate that α‐Sat RNAs have regulatory roles in mitosis. Finally, we explored the transcriptional regulation of α‐Satellite DNA. Through in silico analyses, we detected the presence of CCAAT transcription factor‐binding motifs within α‐Satellite centromeric arrays. Using high‐resolution three‐dimensional immuno‐FISH and ChIP‐qPCR, we showed an association between the α‐Satellite upregulation and the recruitment of the transcription factor NFY‐A to the centromere upon MG132‐induced proteasome inhibition. Together, our results show that the proteasome controls α‐Satellite RNAs associated with the regulation of mitosis. John Wiley and Sons Inc. 2021-11-18 2022-04 /pmc/articles/PMC9299679/ /pubmed/34739170 http://dx.doi.org/10.1111/febs.16261 Text en © 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Cáceres‐Gutiérrez, Rodrigo E. Andonegui, Marco A. Oliva‐Rico, Diego A. González‐Barrios, Rodrigo Luna, Fernando Arriaga‐Canon, Cristian López‐Saavedra, Alejandro Prada, Diddier Castro, Clementina Parmentier, Laurent Díaz‐Chávez, José Alfaro‐Mora, Yair Navarro‐Delgado, Erick I. Fabian‐Morales, Eunice Tran, Bao Shetty, Jyoti Zhao, Yongmei Alcaraz, Nicolas De la Rosa, Carlos Reyes, José L. Hédouin, Sabrine Hubé, Florent Francastel, Claire Herrera, Luis A. Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs |
title | Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs |
title_full | Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs |
title_fullStr | Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs |
title_full_unstemmed | Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs |
title_short | Proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐Satellite RNAs |
title_sort | proteasome inhibition alters mitotic progression through the upregulation of centromeric α‐satellite rnas |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299679/ https://www.ncbi.nlm.nih.gov/pubmed/34739170 http://dx.doi.org/10.1111/febs.16261 |
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