A Splicing-Independent Function of SF2/ASF in MicroRNA Processing

Han Wu, Shuying Sun, Kang Tu, Yuan Gao, Bin Xie, Adrian R. Krainer, Jun Zhu

Research output: Contribution to journalArticlepeer-review

Abstract

Both splicing factors and microRNAs are important regulatory molecules that play key roles in posttranscriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of the splicing factor SF2/ASF. Here we show that SF2/ASF and one of its upregulated microRNAs (miR-7) can form a negative feedback loop: SF2/ASF promotes miR-7 maturation, and mature miR-7 in turn targets the 3′UTR of SF2/ASF to repress its translation. Enhanced microRNA expression is mediated by direct interaction between SF2/ASF and the primary miR-7 transcript to facilitate Drosha cleavage and is independent of SF2/ASF's function in splicing. Other miRNAs, including miR-221 and miR-222, may also be regulated by SF2/ASF through a similar mechanism. These results underscore a function of SF2/ASF in pri-miRNA processing and highlight the potential coordination between splicing control and miRNA-mediated gene repression in gene regulatory networks.

Original languageEnglish (US)
Pages (from-to)67-77
Number of pages11
JournalMolecular cell
Volume38
Issue number1
DOIs
StatePublished - Apr 9 2010
Externally publishedYes

Keywords

  • PROTEINS
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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