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

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 co...

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Detalles Bibliográficos
Autores: Martín García, Elena, 1975-, Vivori, Claudia, 1989-, Rogalska, Malgorzata, Herrero-Vicente, Jorge, Valcárcel, J. (Juan)
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/52825
Acceso en línea:http://hdl.handle.net/10230/52825
http://dx.doi.org/10.1261/rna.078935.121
Access Level:acceso abierto
Palabra clave:Genètica
Cèl·lules -- Proliferació
Càncer
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spelling Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferationMartín García, Elena, 1975-Vivori, Claudia, 1989-Rogalska, MalgorzataHerrero-Vicente, JorgeValcárcel, J. (Juan)GenèticaCèl·lules -- ProliferacióCàncerThe 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.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 CatalunyaCold Spring Harbor Laboratory Press (CSHL Press)202220222021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/52825http://dx.doi.org/10.1261/rna.078935.121reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/EC/H2020/670146info:eu-repo/grantAgreement/ES/2PE/BFU2017-89308-P© 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/http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/528252026-05-29T05:05:01Z
dc.title.none.fl_str_mv Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
title Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
spellingShingle Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
Martín García, Elena, 1975-
Genètica
Cèl·lules -- Proliferació
Càncer
title_short Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
title_full Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
title_fullStr Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
title_full_unstemmed Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
title_sort Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation
dc.creator.none.fl_str_mv Martín García, Elena, 1975-
Vivori, Claudia, 1989-
Rogalska, Malgorzata
Herrero-Vicente, Jorge
Valcárcel, J. (Juan)
author Martín García, Elena, 1975-
author_facet Martín García, Elena, 1975-
Vivori, Claudia, 1989-
Rogalska, Malgorzata
Herrero-Vicente, Jorge
Valcárcel, J. (Juan)
author_role author
author2 Vivori, Claudia, 1989-
Rogalska, Malgorzata
Herrero-Vicente, Jorge
Valcárcel, J. (Juan)
author2_role author
author
author
author
dc.subject.none.fl_str_mv Genètica
Cèl·lules -- Proliferació
Càncer
topic Genètica
Cèl·lules -- Proliferació
Càncer
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/52825
http://dx.doi.org/10.1261/rna.078935.121
url http://hdl.handle.net/10230/52825
http://dx.doi.org/10.1261/rna.078935.121
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/H2020/670146
info:eu-repo/grantAgreement/ES/2PE/BFU2017-89308-P
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press (CSHL Press)
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press (CSHL Press)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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