The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis

Autores
Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M.; Muñoz, Manuel Javier; Botti, Flavia; Kornblihtt, Alberto Rodolfo; Sette, Claudio
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5 splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. Synopsis The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival. The transcription factor FBI-1 directly interacts with the splicing regulator SAM68. FBI-1 impairs binding of SAM68 to BCL-X mRNA and thus promotes production of the anti-apoptotic BCL-X isoform and cell survival. FBI-1's effect on BCL-X splicing requires histone deacetylase activity. The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival.
Fil: Bielli, Pamela. Universita Tor Vergata; Italia. Fondazione Santa Lucia; Italia
Fil: Busà, Roberta. Universita Tor Vergata; Italia. Fondazione Santa Lucia; Italia
Fil: Di Stasi, Savino M.. Universita Tor Vergata; Italia
Fil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Botti, Flavia. Universita Tor Vergata; Italia
Fil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Sette, Claudio. Universita Tor Vergata; Italia. Fondazione Santa Lucia; Italia
Materia
ALTERNATIVE SPLICING
APOPTOSIS
BCL-X
FBI-1
SAM68
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/85073
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosisBielli, PamelaBusà, RobertaDi Stasi, Savino M.Muñoz, Manuel JavierBotti, FlaviaKornblihtt, Alberto RodolfoSette, ClaudioALTERNATIVE SPLICINGAPOPTOSISBCL-XFBI-1SAM68https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5 splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. Synopsis The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival. The transcription factor FBI-1 directly interacts with the splicing regulator SAM68. FBI-1 impairs binding of SAM68 to BCL-X mRNA and thus promotes production of the anti-apoptotic BCL-X isoform and cell survival. FBI-1's effect on BCL-X splicing requires histone deacetylase activity. The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival.Fil: Bielli, Pamela. Universita Tor Vergata; Italia. Fondazione Santa Lucia; ItaliaFil: Busà, Roberta. Universita Tor Vergata; Italia. Fondazione Santa Lucia; ItaliaFil: Di Stasi, Savino M.. Universita Tor Vergata; ItaliaFil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Botti, Flavia. Universita Tor Vergata; ItaliaFil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Sette, Claudio. Universita Tor Vergata; Italia. Fondazione Santa Lucia; ItaliaNature Publishing Group2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentimage/pngapplication/pdfhttp://hdl.handle.net/11336/85073Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M.; Muñoz, Manuel Javier; Botti, Flavia; et al.; The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis; Nature Publishing Group; Embo Reports; 15; 4; 2-2014; 419-4271469-221XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/embr.201338241info:eu-repo/semantics/altIdentifier/url/https://www.embopress.org/doi/10.1002/embr.201338241info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:54:07Zoai:ri.conicet.gov.ar:11336/85073instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:54:08.144CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
title The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
spellingShingle The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
Bielli, Pamela
ALTERNATIVE SPLICING
APOPTOSIS
BCL-X
FBI-1
SAM68
title_short The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
title_full The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
title_fullStr The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
title_full_unstemmed The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
title_sort The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
dc.creator.none.fl_str_mv Bielli, Pamela
Busà, Roberta
Di Stasi, Savino M.
Muñoz, Manuel Javier
Botti, Flavia
Kornblihtt, Alberto Rodolfo
Sette, Claudio
author Bielli, Pamela
author_facet Bielli, Pamela
Busà, Roberta
Di Stasi, Savino M.
Muñoz, Manuel Javier
Botti, Flavia
Kornblihtt, Alberto Rodolfo
Sette, Claudio
author_role author
author2 Busà, Roberta
Di Stasi, Savino M.
Muñoz, Manuel Javier
Botti, Flavia
Kornblihtt, Alberto Rodolfo
Sette, Claudio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ALTERNATIVE SPLICING
APOPTOSIS
BCL-X
FBI-1
SAM68
topic ALTERNATIVE SPLICING
APOPTOSIS
BCL-X
FBI-1
SAM68
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5 splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. Synopsis The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival. The transcription factor FBI-1 directly interacts with the splicing regulator SAM68. FBI-1 impairs binding of SAM68 to BCL-X mRNA and thus promotes production of the anti-apoptotic BCL-X isoform and cell survival. FBI-1's effect on BCL-X splicing requires histone deacetylase activity. The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival.
Fil: Bielli, Pamela. Universita Tor Vergata; Italia. Fondazione Santa Lucia; Italia
Fil: Busà, Roberta. Universita Tor Vergata; Italia. Fondazione Santa Lucia; Italia
Fil: Di Stasi, Savino M.. Universita Tor Vergata; Italia
Fil: Muñoz, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Botti, Flavia. Universita Tor Vergata; Italia
Fil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Sette, Claudio. Universita Tor Vergata; Italia. Fondazione Santa Lucia; Italia
description Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5 splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. Synopsis The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival. The transcription factor FBI-1 directly interacts with the splicing regulator SAM68. FBI-1 impairs binding of SAM68 to BCL-X mRNA and thus promotes production of the anti-apoptotic BCL-X isoform and cell survival. FBI-1's effect on BCL-X splicing requires histone deacetylase activity. The oncogenic transcription factor FBI-1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL-X mRNA. This increases anti-apoptotic BCL-X isoform expression and cell survival.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/85073
Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M.; Muñoz, Manuel Javier; Botti, Flavia; et al.; The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis; Nature Publishing Group; Embo Reports; 15; 4; 2-2014; 419-427
1469-221X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85073
identifier_str_mv Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M.; Muñoz, Manuel Javier; Botti, Flavia; et al.; The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis; Nature Publishing Group; Embo Reports; 15; 4; 2-2014; 419-427
1469-221X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/embr.201338241
info:eu-repo/semantics/altIdentifier/url/https://www.embopress.org/doi/10.1002/embr.201338241
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
image/png
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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