Proteasome inhibition alters mitotic progression through the upregulation of centromeric alpha-Satellite RNAs
Por:
Caceres-Gutierrez, Rodrigo E., Andonegui, Marco A., Oliva-Rico, Diego A., Gonzalez-Barrios, Rodrigo, Luna, Fernando, Arriaga-Canon, Cristian, Lopez-Saavedra, Alejandro, Prada, Diddier, Castro, Clementina, Parmentier, Laurent, Diaz-Chavez, Jose, Alfaro-Mora, Yair, Navarro-Delgado, I, Erick, Fabian-Morales, Eunice, Tran, Bao, Shetty, Jyoti, Zhao, Yongmei, Alcaraz, Nicolas, De la Rosa, Carlos, Reyes, Jose L., Hedouin, Sabrine, Hube, Florent, Francastel, Claire, Herrera, Luis A.
Publicada:
1 abr 2022
Ahead of Print:
1 nov 2021
Resumen:
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 a-Satellite
RNAs. We showed that alpha-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 alpha-Sat RNAs have regulatory roles in
mitosis. Finally, we explored the transcriptional regulation of
alpha-Satellite DNA. Through in silico analyses, we detected the
presence of CCAAT transcription factor-binding motifs within
alpha-Satellite centromeric arrays. Using high-resolution
three-dimensional immuno-FISH and ChIP-qPCR, we showed an association
between the alpha-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 alpha-Satellite RNAs associated with the regulation of mitosis.
Filiaciones:
Caceres-Gutierrez, Rodrigo E.:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Andonegui, Marco A.:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Oliva-Rico, Diego A.:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Gonzalez-Barrios, Rodrigo:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Luna, Fernando:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Arriaga-Canon, Cristian:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Lopez-Saavedra, Alejandro:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Prada, Diddier:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Departamento de Informática Biomédica, Faculty of Medicine, UNAM, Universidad Nacional Autónoma de México, Mexico City, Mexico
Castro, Clementina:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Parmentier, Laurent:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Diaz-Chavez, Jose:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Alfaro-Mora, Yair:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Navarro-Delgado, I, Erick:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Fabian-Morales, Eunice:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Tran, Bao:
NCI CCR Sequencing Facility, Frederick National Laboratory for Cancer ResearchMD, United States
Shetty, Jyoti:
NCI CCR Sequencing Facility, Frederick National Laboratory for Cancer ResearchMD, United States
Zhao, Yongmei:
NCI CCR Sequencing Facility, Frederick National Laboratory for Cancer ResearchMD, United States
Alcaraz, Nicolas:
The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark
National Institute of Genomic Medicine, Mexico City, Mexico
De la Rosa, Carlos:
Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico
Reyes, Jose L.:
Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico
Hedouin, Sabrine:
Epigenetics and Cell Fate, CNRS UMR7216, Université de Paris, Paris, France
Basic Sciences Division, Fred Hutchinson Cancer Research, Seattle, WA, United States
Hube, Florent:
Epigenetics and Cell Fate, CNRS UMR7216, Université de Paris, Paris, France
Francastel, Claire:
Epigenetics and Cell Fate, CNRS UMR7216, Université de Paris, Paris, France
Herrera, Luis A.:
Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Unidad de Investigación Biomédica en Cáncer, Mexico City, Mexico
Dirección General, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Green Published, All Open Access; Hybrid Gold
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