SF2/ASF autoregulation involves multiple layers of post-transcriptional and translational control

Sun, S., Zhang, Z., Sinha, R., Karni, R., Krainer, A. R. (2010) SF2/ASF autoregulation involves multiple layers of post-transcriptional and translational control. Nat Struct Mol Biol, 17 (3). pp. 306-12. ISSN 1545-9985 (Electronic) 1545-9985 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/20139984
DOI: 10.1038/nsmb.1750

Abstract

SF2/ASF is a prototypical serine- and arginine-rich protein, with important roles in splicing and other aspects of mRNA metabolism. Splicing factor, arginine/serine-rich 1 (SFRS1), the gene encoding SF2/ASF, is a potent proto-oncogene with abnormal expression in many tumors. We found that SF2/ASF negatively autoregulates its expression to maintain homeostatic levels. We characterized six alternatively spliced SF2/ASF mRNA isoforms: the major isoform encodes full-length protein, whereas the others are either retained in the nucleus or degraded by nonsense-mediated mRNA decay. Unproductive splicing accounts for only part of the autoregulation, which occurs primarily at the translational level. The effect is specific to SF2/ASF and requires RNA recognition motif 2 (RRM2). The ultraconserved 3' untranslated region (UTR) is necessary and sufficient for downregulation. SF2/ASF overexpression shifts the distribution of target mRNA toward monoribosomes, and translational repression is partly independent of Dicer and a 5' cap. Thus, multiple post-transcriptional and translational mechanisms are involved in fine-tuning the expression of SF2/ASF.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > dicer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > dicer

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
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 > Instrumentation Service
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: CSHL Librarian
Date Deposited: 19 Oct 2011 13:58
Last Modified: 30 Dec 2014 16:39
PMCID: PMC2921916
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15535

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving