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Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells.

2014-02-18Journal article Restricted access
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dc.contributor.authorGonçalves, Vânia
dc.contributor.authorHenriques, Andreia
dc.contributor.authorPereira, Joana
dc.contributor.authorNeves-Costa, Ana
dc.contributor.authorMoyer, Pat
dc.contributor.authorFerreira Moita, Luís
dc.contributor.authorGama-Carvalho, Margarida
dc.contributor.authorMatos, Paulo
dc.contributor.authorJordan, Peter
dc.date.accessioned2014-12-04T14:55:41Z
dc.date.available2014-12-04T14:55:41Z
dc.date.issued2014-02-18
dc.description.abstractAbstract: The premessenger RNA of the majority of human genes can generate various transcripts through alternative splicing, and different tissues or disease states show specific patterns of splicing variants. These patterns depend on the relative concentrations of the splicing factors present in the cell nucleus, either as a consequence of their expression levels or of post-translational modifications, such as protein phosphorylation, which are determined by signal transduction pathways. Here, we analyzed the contribution of protein kinases to the regulation of alternative splicing variant Rac1b that is overexpressed in certain tumor types. In colorectal cells, we found that depletion of AKT2, AKT3, GSK3β, and SRPK1 significantly decreased endogenous Rac1b levels. Although knockdown of AKT2 and AKT3 affected only Rac1b protein levels suggesting a post-splicing effect, the depletion of GSK3β or SRPK1 decreased Rac1b alternative splicing, an effect mediated through changes in splicing factor SRSF1. In particular, the knockdown of SRPK1 or inhibition of its catalytic activity reduced phosphorylation and subsequent translocation of SRSF1 to the nucleus, limiting its availability to promote the inclusion of alternative exon 3b into the Rac1 pre-mRNA. Altogether, the data identify SRSF1 as a prime regulator of Rac1b expression in colorectal cells and provide further mechanistic insight into how the regulation of alternative splicing events by protein kinases can contribute to sustain tumor cell survival.por
dc.description.sponsorshipThis work was supported by the Fundação para a Ciência e Tecnologia, Portugal (Grants PEstOE/BIA/UI4046/2011 to the BioFig research unit, and PTDC/SAUMII/100780/2008 and PTDC/SAU-IMU/110303/2009 to L.F.M, contract Ciência2007 to P.M., and fellowship BPD 63395/2009 to V.G). L.F.M. received support from Fundação Luso-Americana para o Desenvolvimento.por
dc.identifier.citationRNA. 2014 Apr;20(4):474-82. doi: 10.1261/rna.041376.113. Epub 2014 Feb 18por
dc.identifier.doi10.1261/rna.041376.113
dc.identifier.issn1355-8382
dc.identifier.urihttp://hdl.handle.net/10400.18/2520
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherCold Spring Harbor Laboratory Press/ RNA Societypor
dc.relation.publisherversionhttp://rnajournal.cshlp.org/content/20/4/474.abstractpor
dc.subjectVias de Transdução de Sinal e Patologias Associadaspor
dc.subjectAlternative Splicingpor
dc.subjectPhosphorylationpor
dc.subjectRac1bpor
dc.subjectSRSF1por
dc.subjectSRPK1por
dc.titlePhosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells.por
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage482por
oaire.citation.startPage474por
oaire.citation.titleRNApor
oaire.citation.volume20(4)por
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor

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