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

Shuying Sun, Zuo Zhang, Rahul Sinha, Rotem Karni, Adrian R. Krainer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)306-312
Number of pages7
JournalNature Structural and Molecular Biology
Volume17
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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