The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators

Autores
Llorian, Miriam; Gooding, Clare; Bellora, Nicolás; Hallegger, Martina; Buckroyd, Adrian; Wang, Xiao; Rajgor, Dipen; Kayikci, Melis; Feltham, Jack; Ule, Jernej; Eyras, Eduardo; Smith, Christopher
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alternative splicing (AS) is a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1). Consistent with this, knockdown experiments showed that that PTBP1 represses many smooth muscle specific exons. We also observed coordinated splicing changes predicted to downregulate the expression of core components of U1 and U2 snRNPs, splicing regulators and other post-transcriptional factors in differentiated cells. The levels of cognate proteins were lower or similar in differentiated compared to undifferentiated cells. However, levels of snRNAs did not follow the expression of splicing proteins, and in the case of U1 snRNP we saw reciprocal changes in the levels of U1 snRNA and U1 snRNP proteins. Our results suggest that the AS program in differentiated SMCs is orchestrated by the combined influence of auxiliary RNA binding proteins, such as PTBP1, along with altered activity and stoichiometry of the core splicing machinery.
Fil: Llorian, Miriam. University of Cambridge; Reino Unido
Fil: Gooding, Clare. University of Cambridge; Reino Unido
Fil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. University College London; Reino Unido. Institució Catalana de Recerca i Estudis Avancats; España
Fil: Hallegger, Martina. University College London; Estados Unidos. Universitat Pompeu Fabra; España
Fil: Buckroyd, Adrian. University College London; Reino Unido
Fil: Wang, Xiao. University of Cambridge; Reino Unido
Fil: Rajgor, Dipen. University of Cambridge; Reino Unido
Fil: Kayikci, Melis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina
Fil: Feltham, Jack. University of Cambridge; Reino Unido
Fil: Ule, Jernej. Universitat Pompeu Fabra; España
Fil: Eyras, Eduardo. MRC-Laboratory of Molecular Biology; Reino Unido. University College London; Reino Unido
Fil: Smith, Christopher. University of Cambridge; Reino Unido
Materia
Alternative splicing
Cellular differentiation
Bioinformatics
Gene expression
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/74313
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/74313
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulatorsLlorian, MiriamGooding, ClareBellora, NicolásHallegger, MartinaBuckroyd, AdrianWang, XiaoRajgor, DipenKayikci, MelisFeltham, JackUle, JernejEyras, EduardoSmith, ChristopherAlternative splicingCellular differentiationBioinformaticsGene expressionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alternative splicing (AS) is a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1). Consistent with this, knockdown experiments showed that that PTBP1 represses many smooth muscle specific exons. We also observed coordinated splicing changes predicted to downregulate the expression of core components of U1 and U2 snRNPs, splicing regulators and other post-transcriptional factors in differentiated cells. The levels of cognate proteins were lower or similar in differentiated compared to undifferentiated cells. However, levels of snRNAs did not follow the expression of splicing proteins, and in the case of U1 snRNP we saw reciprocal changes in the levels of U1 snRNA and U1 snRNP proteins. Our results suggest that the AS program in differentiated SMCs is orchestrated by the combined influence of auxiliary RNA binding proteins, such as PTBP1, along with altered activity and stoichiometry of the core splicing machinery.Fil: Llorian, Miriam. University of Cambridge; Reino UnidoFil: Gooding, Clare. University of Cambridge; Reino UnidoFil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. University College London; Reino Unido. Institució Catalana de Recerca i Estudis Avancats; EspañaFil: Hallegger, Martina. University College London; Estados Unidos. Universitat Pompeu Fabra; EspañaFil: Buckroyd, Adrian. University College London; Reino UnidoFil: Wang, Xiao. University of Cambridge; Reino UnidoFil: Rajgor, Dipen. University of Cambridge; Reino UnidoFil: Kayikci, Melis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Feltham, Jack. University of Cambridge; Reino UnidoFil: Ule, Jernej. Universitat Pompeu Fabra; EspañaFil: Eyras, Eduardo. MRC-Laboratory of Molecular Biology; Reino Unido. University College London; Reino UnidoFil: Smith, Christopher. University of Cambridge; Reino UnidoOxford University Press2016-10-17info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/74313Llorian, Miriam; Gooding, Clare; Bellora, Nicolás; Hallegger, Martina; Buckroyd, Adrian; et al.; The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators; Oxford University Press; Nucleic Acids Research; 44; 18; 17-10-2016; 8933-89500305-10481362-4962CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://nar.oxfordjournals.org/content/early/2016/06/17/nar.gkw560.full.pdf+htmlinfo:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkw560info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/44/18/8933/2468335info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:13:18Zoai:ri.conicet.gov.ar:11336/74313instacron: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 10:13:19.097CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
title The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
spellingShingle The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
Llorian, Miriam
Alternative splicing
Cellular differentiation
Bioinformatics
Gene expression
title_short The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
title_full The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
title_fullStr The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
title_full_unstemmed The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
title_sort The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
dc.creator.none.fl_str_mv Llorian, Miriam
Gooding, Clare
Bellora, Nicolás
Hallegger, Martina
Buckroyd, Adrian
Wang, Xiao
Rajgor, Dipen
Kayikci, Melis
Feltham, Jack
Ule, Jernej
Eyras, Eduardo
Smith, Christopher
author Llorian, Miriam
author_facet Llorian, Miriam
Gooding, Clare
Bellora, Nicolás
Hallegger, Martina
Buckroyd, Adrian
Wang, Xiao
Rajgor, Dipen
Kayikci, Melis
Feltham, Jack
Ule, Jernej
Eyras, Eduardo
Smith, Christopher
author_role author
author2 Gooding, Clare
Bellora, Nicolás
Hallegger, Martina
Buckroyd, Adrian
Wang, Xiao
Rajgor, Dipen
Kayikci, Melis
Feltham, Jack
Ule, Jernej
Eyras, Eduardo
Smith, Christopher
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alternative splicing
Cellular differentiation
Bioinformatics
Gene expression
topic Alternative splicing
Cellular differentiation
Bioinformatics
Gene expression
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 a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1). Consistent with this, knockdown experiments showed that that PTBP1 represses many smooth muscle specific exons. We also observed coordinated splicing changes predicted to downregulate the expression of core components of U1 and U2 snRNPs, splicing regulators and other post-transcriptional factors in differentiated cells. The levels of cognate proteins were lower or similar in differentiated compared to undifferentiated cells. However, levels of snRNAs did not follow the expression of splicing proteins, and in the case of U1 snRNP we saw reciprocal changes in the levels of U1 snRNA and U1 snRNP proteins. Our results suggest that the AS program in differentiated SMCs is orchestrated by the combined influence of auxiliary RNA binding proteins, such as PTBP1, along with altered activity and stoichiometry of the core splicing machinery.
Fil: Llorian, Miriam. University of Cambridge; Reino Unido
Fil: Gooding, Clare. University of Cambridge; Reino Unido
Fil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. University College London; Reino Unido. Institució Catalana de Recerca i Estudis Avancats; España
Fil: Hallegger, Martina. University College London; Estados Unidos. Universitat Pompeu Fabra; España
Fil: Buckroyd, Adrian. University College London; Reino Unido
Fil: Wang, Xiao. University of Cambridge; Reino Unido
Fil: Rajgor, Dipen. University of Cambridge; Reino Unido
Fil: Kayikci, Melis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina
Fil: Feltham, Jack. University of Cambridge; Reino Unido
Fil: Ule, Jernej. Universitat Pompeu Fabra; España
Fil: Eyras, Eduardo. MRC-Laboratory of Molecular Biology; Reino Unido. University College London; Reino Unido
Fil: Smith, Christopher. University of Cambridge; Reino Unido
description Alternative splicing (AS) is a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1). Consistent with this, knockdown experiments showed that that PTBP1 represses many smooth muscle specific exons. We also observed coordinated splicing changes predicted to downregulate the expression of core components of U1 and U2 snRNPs, splicing regulators and other post-transcriptional factors in differentiated cells. The levels of cognate proteins were lower or similar in differentiated compared to undifferentiated cells. However, levels of snRNAs did not follow the expression of splicing proteins, and in the case of U1 snRNP we saw reciprocal changes in the levels of U1 snRNA and U1 snRNP proteins. Our results suggest that the AS program in differentiated SMCs is orchestrated by the combined influence of auxiliary RNA binding proteins, such as PTBP1, along with altered activity and stoichiometry of the core splicing machinery.
publishDate 2016
dc.date.none.fl_str_mv 2016-10-17
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/11336/74313
Llorian, Miriam; Gooding, Clare; Bellora, Nicolás; Hallegger, Martina; Buckroyd, Adrian; et al.; The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators; Oxford University Press; Nucleic Acids Research; 44; 18; 17-10-2016; 8933-8950
0305-1048
1362-4962
CONICET Digital
CONICET
url http://hdl.handle.net/11336/74313
identifier_str_mv Llorian, Miriam; Gooding, Clare; Bellora, Nicolás; Hallegger, Martina; Buckroyd, Adrian; et al.; The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators; Oxford University Press; Nucleic Acids Research; 44; 18; 17-10-2016; 8933-8950
0305-1048
1362-4962
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://nar.oxfordjournals.org/content/early/2016/06/17/nar.gkw560.full.pdf+html
info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gkw560
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/44/18/8933/2468335
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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score 13.070432

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