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dc.contributor.author
Llorian, Miriam
dc.contributor.author
Gooding, Clare
dc.contributor.author
Bellora, Nicolás
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dc.contributor.author
Hallegger, Martina
dc.contributor.author
Buckroyd, Adrian
dc.contributor.author
Wang, Xiao
dc.contributor.author
Rajgor, Dipen
dc.contributor.author
Kayikci, Melis
dc.contributor.author
Feltham, Jack
dc.contributor.author
Ule, Jernej
dc.contributor.author
Eyras, Eduardo
dc.contributor.author
Smith, Christopher
dc.date.available
2019-04-12T20:51:33Z
dc.date.issued
2016-10-17
dc.identifier.citation
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
dc.identifier.issn
0305-1048
dc.identifier.uri
http://hdl.handle.net/11336/74313
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Alternative Splicing
dc.subject
Cellular Differentiation
dc.subject
Bioinformatics
dc.subject
Gene Expression
dc.subject.classification
Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-02-12T16:55:57Z
dc.identifier.eissn
1362-4962
dc.journal.volume
44
dc.journal.number
18
dc.journal.pagination
8933-8950
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Oxford
dc.description.fil
Fil: Llorian, Miriam. University of Cambridge; Reino Unido
dc.description.fil
Fil: Gooding, Clare. University of Cambridge; Reino Unido
dc.description.fil
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
dc.description.fil
Fil: Hallegger, Martina. University College London; Estados Unidos. Universitat Pompeu Fabra; España
dc.description.fil
Fil: Buckroyd, Adrian. University College London; Reino Unido
dc.description.fil
Fil: Wang, Xiao. University of Cambridge; Reino Unido
dc.description.fil
Fil: Rajgor, Dipen. University of Cambridge; Reino Unido
dc.description.fil
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
dc.description.fil
Fil: Feltham, Jack. University of Cambridge; Reino Unido
dc.description.fil
Fil: Ule, Jernej. Universitat Pompeu Fabra; España
dc.description.fil
Fil: Eyras, Eduardo. MRC-Laboratory of Molecular Biology; Reino Unido. University College London; Reino Unido
dc.description.fil
Fil: Smith, Christopher. University of Cambridge; Reino Unido
dc.journal.title
Nucleic Acids Research
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://nar.oxfordjournals.org/content/early/2016/06/17/nar.gkw560.full.pdf+html
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/nar/gkw560
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/44/18/8933/2468335
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