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Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1

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dc.contributor.author Avolio, Rosario
dc.contributor.author Inglés Ferrándiz, Marta, 1989-
dc.contributor.author Ciocia, Annagiulia
dc.contributor.author Coll, Olga
dc.contributor.author Bonnin, Sarah
dc.contributor.author Guitart, Tanit
dc.contributor.author Ribó Rubio, Anna
dc.contributor.author Gebauer, Fátima
dc.date.accessioned 2022-03-29T06:40:53Z
dc.date.available 2022-03-29T06:40:53Z
dc.date.issued 2022
dc.identifier.citation Avolio R, Inglés-Ferrándiz M, Ciocia A, Coll O, Bonnin S, Guitart T, Ribó A, Gebauer F. Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1. Cell Rep. 2022 Jan 11;38(2):110211. DOI: 10.1016/j.celrep.2021.110211
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/52785
dc.description.abstract Oncogene-induced senescence (OIS) is a form of stable cell-cycle arrest arising in response to oncogenic stimulation. OIS must be bypassed for transformation, but the mechanisms of OIS establishment and bypass remain poorly understood, especially at the post-transcriptional level. Here, we show that the RNA-binding protein UNR/CSDE1 enables OIS in primary mouse keratinocytes. Depletion of CSDE1 leads to senescence bypass, cell immortalization, and tumor formation, indicating that CSDE1 behaves as a tumor suppressor. Unbiased high-throughput analyses uncovered that CSDE1 promotes OIS by two independent molecular mechanisms: enhancement of the stability of senescence-associated secretory phenotype (SASP) factor mRNAs and repression of Ybx1 mRNA translation. Importantly, depletion of YBX1 from immortal keratinocytes rescues senescence and uncouples proliferation arrest from the SASP, revealing multilayered mechanisms exerted by CSDE1 to coordinate senescence. Our data highlight the relevance of post-transcriptional control in the regulation of senescence.
dc.description.sponsorship We thank Bill Keyes and members of his lab Mekayla Storer, Birgit Ritschka, and Alba Mas for expert advice and help at the initial stages of this project. We also thank Jernej Ule for sharing reagents and expertise on iCLIP, Ola Larsson for guidance on anota2seq, and Bill Keyes and Juan Valcárcel for carefully reading the manuscript. We acknowledge Raquel García Olivas of the CRG Advanced Light Microscopy Unit (ALMU) for her support and assistance in this work. We thank the CRG Bioinformatics Unit, the CRG Genomics Facility, the CRG/UPF FACS Unit, and the IRB Histopathology Facility for high-throughput sequencing and analysis, cell sorting, and histopathology analysis, respectively. M.I.-F. and A.C. were supported by FPI fellowships from the Spanish Ministry of Science and Innovation (MICINN) . F.G. was supported by grants from MICINN ( PGC2018-099697-B-I00 and BFU2015-68741 ), “La Caixa” Foundation (ID 100010434 ) under the agreement LCF/PR/HR17/52150016, the Catalan Agency for Research and Universities ( 2017SGR534 ), and the Centre of Excellence Severo Ochoa.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Rep. 2022 Jan 11;38(2):110211
dc.rights © 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2021.110211
dc.subject.keyword CSDE1
dc.subject.keyword H-Ras(V12)
dc.subject.keyword SASP
dc.subject.keyword UNR
dc.subject.keyword YBX1
dc.subject.keyword mRNA stability
dc.subject.keyword Oncogene-induced senescence
dc.subject.keyword Post-transcriptional regulation
dc.subject.keyword Primary mouse keratinocytes
dc.subject.keyword Translational control
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099697-B-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68741
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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