Rbfox3 controls the biogenesis of a subset of microRNAs

Kee K. Kim, Yanqin Yang, Jun Zhu, Robert S. Adelstein, Sachiyo Kawamoto

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


RNA-binding proteins (RBPs) regulate numerous aspects of gene expression; thus, identification of their endogenous targets is important for understanding their cellular functions. Here we identified transcriptome-wide targets of Rbfox3 in neuronally differentiated P19 cells and mouse brain by using photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP). Although Rbfox3 is known to regulate pre-mRNA splicing through binding the UGCAUG motif, PAR-CLIP analysis revealed diverse Rbfox3 targets including primary microRNAs (pri-miRNAs) that lack the UGCAUG motif. Induced expression and depletion of Rbfox3 led to changes in the expression levels of a subset of PAR-CLIP-detected miRNAs. In vitro analyses revealed that Rbfox3 functions as a positive and a negative regulator at the stage of pri-miRNA processing to precursor miRNA (pre-miRNA). Rbfox3 binds directly to pri-miRNAs and regulates the recruitment of the microprocessor complex to pri-miRNAs. Our study proposes a new function for Rbfox3 in miRNA biogenesis.

Original languageEnglish
Pages (from-to)901-910
Number of pages10
JournalNature Structural and Molecular Biology
Issue number10
StatePublished - 1 Jan 2014
Externally publishedYes


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