Arginine Methylation Controls the Subcellular Localization and Functions of the Oncoprotein Splicing Factor SF2/ASF

Sinha, R., Allemand, E., Zhang, Z., Karni, R., Myers, M. P., Krainer, A. R. (March 2010) Arginine Methylation Controls the Subcellular Localization and Functions of the Oncoprotein Splicing Factor SF2/ASF. Molecular and Cellular Biology, 30 (11). pp. 2762-2774. ISSN 0270-7306

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URL: http://www.ncbi.nlm.nih.gov/pubmed/20308322
DOI: 10.1128/MCB.01270-09

Abstract

Alternative splicing and post-translational modifications (PTMs) are major sources of protein diversity in eukaryotic proteomes. The SR protein SF2/ASF is an oncoprotein that functions in pre-mRNA splicing, with additional roles in other post-transcriptional and translational events. Functional studies of SR-protein PTMs have exclusively focused on reversible phosphorylation of Ser residues in the C-terminal RS domain. We confirmed that human SF2/ASF is methylated at residues R93, R97, and R109, which were identified in a global proteomic analysis of Arg methylation, and further investigated whether these methylated residues regulate the properties of SF2/ASF. We show that the three arginines additively control the subcellular localization of SF2/ASF, and both the positive charge and the methylation state are important. Mutations that block methylation and remove the positive charge result in cytoplasmic accumulation of SF2/ASF. The consequent decrease in nuclear SF2/ASF levels prevents it from modulating alternative splicing of target genes, results in higher translation stimulation, and abrogates the enhancement of nonsense-mediated mRNA decay. This study addresses the mechanisms by which Arg methylation and the associated positive charge regulate the activities of SF2/ASF, and emphasizes the significance of localization control for an oncoprotein with multiple functions in different cellular compartments.

Item Type: Paper
Uncontrolled Keywords: Alternative splicing post-translational modification PTMs eukaryotic proteomes SF2/ASF Arg methylation
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > post-translational modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation
CSHL Authors:
Communities: CSHL labs > Krainer lab
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
Depositing User: CSHL Librarian
Date: 22 March 2010
Date Deposited: 19 Oct 2011 14:23
Last Modified: 30 Dec 2014 16:37
PMCID: PMC2876523
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15531

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