microRNA sequencing after over-expression of SF2/ASF in Hela cell. Homo sapiens

Both splicing factors and microRNAs are important regulatory molecules that play key roles in post-transcriptional gene regulation. By miRNA deep sequencing, we identified 40 miRNAs that are differentially expressed upon ectopic overexpression of splicing factor SF2/ASF. Here we show that SF2/ASF and one of its up-regulated 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 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 an unexpected 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.