Molecular Cell
Volume 38, Issue 1, 9 April 2010, Pages 67-77
Journal home page for Molecular Cell

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

https://doi.org/10.1016/j.molcel.2010.02.021 Get rights and content
Under an Elsevier user license
open archive

Summary

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.

Highlights

► Mature miR-7 is upregulated by ectopic expression of splicing factor SF2/ASF ► Reciprocal targeting between SF2/ASF and miR-7 to form a negative feedback circuit ► A splicing-independent function of SF2/ASF in pri-miR-7 maturation ► SF2/ASF directly binds to primary miRNA transcripts and promotes Drosha cleavage

RNA
PROTEINS

Cited by (0)