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- Title
SF2/ASF autoregulation involves multiple layers of post-transcriptional and translational control.
- Authors
Shuying Sun; Zuo Zhang; Sinha, Rahul; Karni, Rotem; Krainer, Adrian R.
- 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.
- Subjects
SERINE; ARGININE; AMINO acids; MESSENGER RNA; RIBOSOMES
- Publication
Nature Structural & Molecular Biology, 2010, Vol 17, Issue 3, p306
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.1750