Rbfox2 controls autoregulation in RNA binding protein networks

We generated a global analysis of Rbfox2 splicing regulation combined with a highly specific, single nucleotide-resolution Rbfox2 RNA binding map. We found that Rbfox2 regulates the splicing and expression of many previously unknown targets, and particularly a number of RNA binding proteins (RBPs), by modulating alternative splicing coupled-NMD. Based on our observations of RBP-Rbfox2 co-regulation with a polarity predicted by Rbfox2 binding, we propose a model whereby Rbfox2 tunes autoregulatory splicing events to control RBP expression levels and in turn alter their respective splicing networks. Overall design: iCLIP for epitope-tagged Rbfox2 and control untagged Rbfox2; RNAseq of control and Rbfox2 knockdown in mouse embryonic stem cells

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Jangi M, Boutz PL, Paul P, Sharp PA