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

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 nuc...

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Autores principales: Gonçalves, Vânia, Henriques, Andreia, Pereira, Joana, Neves Costa, Ana, Moyer, Mary Pat, Moita, Luís Ferreira, Gama-Carvalho, Margarida, Matos, Paulo, Jordan, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964909/
https://www.ncbi.nlm.nih.gov/pubmed/24550521
http://dx.doi.org/10.1261/rna.041376.113
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author Gonçalves, Vânia
Henriques, Andreia
Pereira, Joana
Neves Costa, Ana
Moyer, Mary Pat
Moita, Luís Ferreira
Gama-Carvalho, Margarida
Matos, Paulo
Jordan, Peter
author_facet Gonçalves, Vânia
Henriques, Andreia
Pereira, Joana
Neves Costa, Ana
Moyer, Mary Pat
Moita, Luís Ferreira
Gama-Carvalho, Margarida
Matos, Paulo
Jordan, Peter
author_sort Gonçalves, Vânia
collection PubMed
description 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.
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spelling pubmed-39649092015-04-01 Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells Gonçalves, Vânia Henriques, Andreia Pereira, Joana Neves Costa, Ana Moyer, Mary Pat Moita, Luís Ferreira Gama-Carvalho, Margarida Matos, Paulo Jordan, Peter RNA Articles 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. Cold Spring Harbor Laboratory Press 2014-04 /pmc/articles/PMC3964909/ /pubmed/24550521 http://dx.doi.org/10.1261/rna.041376.113 Text en © 2014 Gonçalves et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Articles
Gonçalves, Vânia
Henriques, Andreia
Pereira, Joana
Neves Costa, Ana
Moyer, Mary Pat
Moita, Luís Ferreira
Gama-Carvalho, Margarida
Matos, Paulo
Jordan, Peter
Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
title Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
title_full Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
title_fullStr Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
title_full_unstemmed Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
title_short Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
title_sort phosphorylation of srsf1 by srpk1 regulates alternative splicing of tumor-related rac1b in colorectal cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964909/
https://www.ncbi.nlm.nih.gov/pubmed/24550521
http://dx.doi.org/10.1261/rna.041376.113
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