Evidence map›Paper›PMID 24550521›Full record

ArticleRNA (New York, N.Y.)2014

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

Vânia Gonçalves, Andreia F A Henriques, Andreia Henriques, Joana F S Pereira, Joana Pereira, Ana Neves Costa, Mary Pat Moyer, Luís Ferreira Moita, Margarida Gama-Carvalho, Paulo Matos and 1 more

Erratum issuedAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 1 synthesis or guideline pooled it.

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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Vânia Gonçalves
Andreia F A Henriques
Andreia Henriques
Joana F S Pereira
Joana Pereira
Ana Neves Costa
Mary Pat Moyer
Luís Ferreira Moita
Margarida Gama-Carvalho
Paulo Matos
Peter Jordan

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Gene Expression Regulation, NeoplasticAlternative SplicingBlotting, WesternCell NucleusColorectal NeoplasmsExonsFluorescent Antibody TechniqueGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMicroscopy, FluorescenceNuclear ProteinsPhosphorylationProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktAKT2 protein, humanAKT3 protein, humanGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanNuclear ProteinsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktrac1 GTP-Binding ProteinRAC1 protein, humanRNA-Binding ProteinsRNA, MessengerRNA, Small InterferingSerine-Arginine Splicing FactorsSRPK1 protein, humanalternative splicingcolorectal cancersignal transduction pathwaysSRPK1SRSF1

Identifiers

PMID24550521
PMCPMC3964909

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.