Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing

Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas.We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x al...

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Autores: Montes, Marta, Coiras, Mayte, Becerra, Soraya, Moreno-Castro, Cristina, Mateos, Elena, Majuelos-Melguizo, Jara, Oliver, Francisco Javier, Hernández-Munaín, Cristina, Alcamí, José, Suñé, Carlos
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/131129
Acceso en línea:http://hdl.handle.net/10261/131129
Access Level:acceso abierto
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spelling Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative SplicingMontes, MartaCoiras, MayteBecerra, SorayaMoreno-Castro, CristinaMateos, ElenaMajuelos-Melguizo, JaraOliver, Francisco JavierHernández-Munaín, CristinaAlcamí, JoséSuñé, CarlosHere, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas.We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness [grant numbers BFU2011-24577 and BFU2014-54660-R] and the Andalusian Government [Excellence Projects CVI-4626/2009 and BIO-2515/2012] to CS; the Spanish Ministry of Economy and Competitiveness [grant number BFU2013-44660-R] and the Andalusian Government [Excellence Project CTS-6587] to CHM; the Spanish Ministry of Economy and Competitiveness [grant numbers SAF2013-44677-R and FIS PI12/00506], the SPANISH AIDS Research Network RD12/0017/ 0015 that is included in Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008-2011, Instituto de Salud Carlos III, European Region Development Fund, ERDF (FEDER) to MC and JA. MM was supported by a fellowship from the Spanish Ministry of Education (FPU program)Peer reviewedPublic Library of ScienceConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201620162015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/131129reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139812#ackSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1311292026-05-22T06:33:51Z
dc.title.none.fl_str_mv Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
spellingShingle Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
Montes, Marta
title_short Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_full Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_fullStr Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_full_unstemmed Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
title_sort Functional Consequences for Apoptosis by Transcription Elongation Regulator 1 (TCERG1)-Mediated Bcl-x and Fas/CD95 Alternative Splicing
dc.creator.none.fl_str_mv Montes, Marta
Coiras, Mayte
Becerra, Soraya
Moreno-Castro, Cristina
Mateos, Elena
Majuelos-Melguizo, Jara
Oliver, Francisco Javier
Hernández-Munaín, Cristina
Alcamí, José
Suñé, Carlos
author Montes, Marta
author_facet Montes, Marta
Coiras, Mayte
Becerra, Soraya
Moreno-Castro, Cristina
Mateos, Elena
Majuelos-Melguizo, Jara
Oliver, Francisco Javier
Hernández-Munaín, Cristina
Alcamí, José
Suñé, Carlos
author_role author
author2 Coiras, Mayte
Becerra, Soraya
Moreno-Castro, Cristina
Mateos, Elena
Majuelos-Melguizo, Jara
Oliver, Francisco Javier
Hernández-Munaín, Cristina
Alcamí, José
Suñé, Carlos
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Here, we present evidence for a specific role of the splicing-related factor TCERG1 in regulating apoptosis in live cells by modulating the alternative splicing of the apoptotic genes Bcl-x and Fas.We show that TCERG1 modulates Bcl-x alternative splicing during apoptosis and its activity in Bcl-x alternative splicing correlates with the induction of apoptosis, as determined by assessing dead cells, sub-G1-phase cells, annexin-V binding, cell viability, and cleavage of caspase-3 and PARP-1. Furthermore, the effect of TCERG1 on apoptosis involved changes in mitochondrial membrane permeabilization. We also found that depletion of TCERG1 reduces the expression of the activated form of the pro-apoptotic mitochondrial membrane protein Bak, which remains inactive by heterodimerizing with Bcl-xL, preventing the initial step of cytochrome c release in Bak-mediated mitochondrial apoptosis. In addition, we provide evidence that TCERG1 also participates in the death receptor-mediated apoptosis pathway. Interestingly, TCERG1 also modulates Fas/CD95 alternative splicing. We propose that TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. Our findings may provide a new link between the control of alternative splicing and the molecular events leading to apoptosis.
publishDate 2015
dc.date.none.fl_str_mv 2015
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/131129
url http://hdl.handle.net/10261/131129
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139812#ack
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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