The Splicing Factor SF2/ASF Regulates Translation Initiation by Enhancing Phosphorylation of 4E-BP1

Gracjan Michlewski, Jeremy R Sanford, Javier F Cáceres

Research output: Contribution to journalArticlepeer-review

Abstract

The SR protein SF2/ASF has been initially characterized as a splicing factor but has also been shown to mediate postsplicing activities such as mRNA export and translation. Here we demonstrate that SF2/ASF promotes translation initiation of bound mRNAs and that this activity requires the presence of the cytoplasmic cap-binding protein eIF4E. SF2/ASF promotes translation initiation by suppressing the activity of 4E-BP, a competitive inhibitor of cap-dependent translation. This activity is mediated by interactions of SF2/ASF with both mTOR and the phosphatase PP2A, two key regulators of 4E-BP phosphorylation. These findings suggest the model whereby SF2/ASF functions as an adaptor protein to recruit the signaling molecules responsible for regulation of cap-dependent translation of specific mRNAs. Taken together, these data suggest a novel mechanism for the activation of translation initiation of a subset of mRNAs bound by the shuttling protein SF2/ASF.
Original languageEnglish
Pages (from-to)179-189
Number of pages11
JournalMolecular Cell
Volume30
Issue number2
DOIs
Publication statusPublished - Apr 2008

Keywords

  • RNA

Fingerprint Dive into the research topics of 'The Splicing Factor SF2/ASF Regulates Translation Initiation by Enhancing Phosphorylation of 4E-BP1'. Together they form a unique fingerprint.

Cite this