Mechanistic analyses of transcriptional regulation via RNA-binding proteins

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A novel coactivator hnRNP R (heterogeneous nuclear ribonucleoprotein R) facilitates transcription reinitiation from the c-fos promoter in vitro in cooperation with Mediator. The cooperative action of hnRNP R and Mediator is diminished by the CDK8 module, which is comprised of CDK8, Cyclin C, MED12, and MED13 of the Mediator subunits. Consistently, hnRNP R interacts with the Scaffold components (Mediator, TBP, and TFIIH) as well as TFIIB, which recruits Pol II and TFIIF to Scaffold. The RNA transcript produced from the G-free cassette interacts with hnRNP R through its RNA recognition motifs (RRMs) and arginine-glycine-glycine (RGG) domain. Knockdown of hnRNP R in mouse cells compromised rapid induction of several immediate-early genes. These results suggest an important role for hnRNP R in regulating robust response of immediate-early genes.