Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation

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  • dc.contributor.author Martín García, Elena, 1975-
  • dc.contributor.author Vivori, Claudia, 1989-
  • dc.contributor.author Rogalska, Malgorzata
  • dc.contributor.author Herrero-Vicente, Jorge
  • dc.contributor.author Valcárcel, J. (Juan)
  • dc.date.accessioned 2022-04-04T10:40:46Z
  • dc.date.available 2022-04-04T10:40:46Z
  • dc.date.issued 2021
  • dc.description.abstract The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation, but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, and CHERP, form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell-cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulates the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.
  • dc.description.sponsorship Funding: E.M. and J.H. are recipients of FPI Fellowships from the Spanish Ministry of Economy and Competitiveness.Work in our laboratory has been supported by the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU2017-89308-P), and the Centre of Excellence Severo Ochoa. We acknowledge suport from the Spanish Ministry of Science and Innovation to the EMBL partnership and the CERCA Programme/Generalitat de Catalunya
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Martín E, Vivori C, Rogalska M, Herrero-Vicente J, Valcárcel J. Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation. RNA. 2021 Dec;27(12):1557-76. DOI: 10.1261/rna.078935.121
  • dc.identifier.doi http://dx.doi.org/10.1261/rna.078935.121
  • dc.identifier.issn 1355-8382
  • dc.identifier.uri http://hdl.handle.net/10230/52825
  • dc.language.iso eng
  • dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670146
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89308-P
  • dc.rights © 2021 Martín et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Cèl·lules -- Proliferació
  • dc.subject.other Càncer
  • dc.title Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion