Mechanisms of activation and repression by the alternative splicing factors RBFOX1/2

Sun, S. Y., Zhang, Z., Fregoso, O., Krainer, A. R. (February 2012) Mechanisms of activation and repression by the alternative splicing factors RBFOX1/2. RNA, 18 (2). pp. 274-283. ISSN 1355-8382

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22184459
DOI: 10.1261/rna.030486.111

Abstract

RBFOX1 and RBFOX2 are alternative splicing factors that are predominantly expressed in the brain and skeletal muscle. They specifically bind the RNA element UGCAUG, and regulate alternative splicing positively or negatively in a position-dependent manner. The molecular basis for the position dependence of these and other splicing factors on alternative splicing of their targets is not known. We explored the mechanisms of RBFOX splicing activation and repression using an MS2-tethering assay. We found that the Ala/Tyr/Gly-rich C-terminal domain is sufficient for exon activation when tethered to the downstream intron, whereas both the C-terminal domain and the central RRM are required for exon repression when tethered to the upstream intron. Using immunoprecipitation and mass spectrometry, we identified hnRNP H1, RALY, and TFG as proteins that specifically interact with the C-terminal domain of RBFOX1 and RBFOX2. RNA interference experiments showed that hnRNP H1 and TFG modulate the splicing activity of RBFOX1/2, whereas RALY had no effect. However, TFG is localized in the cytoplasm, and likely modulates alternative splicing indirectly.

Item Type: Paper
Uncontrolled Keywords: RBFOX alternative splicing hnRNP H1 TFG heterogeneous nuclear ribonucleoprotein messenger-rna hnrnp-h complex-formation sr proteins rs-domain gene exon binding fox-1
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Antibody and Phage Display Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL Cancer Center Shared Resources > Proteomics Service
CSHL labs > Krainer lab
Watson School > Publications
CSHL Cancer Center Shared Resources > Mass Spectrometry Service
Depositing User: Matt Covey
Date: February 2012
Date Deposited: 18 Jan 2013 19:50
Last Modified: 09 Nov 2017 21:19
PMCID: PMC3264914
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27058

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