title: Heterogeneous nuclear ribonucleoprotein R cooperates with mediator to facilitate transcription reinitiation on the c-Fos gene.
abstract: The c-fos gene responds to extracellular stimuli and undergoes robust but transient transcriptional activation. Here we show that heterogeneous nuclear ribonucleoprotein R (hnRNP R) facilitates transcription reinitiation of the c-fos promoter in vitro in cooperation with Mediator. Consistently, hnRNP R interacts with the Scaffold components (Mediator, TBP, and TFIIH) as well as TFIIB, which recruits RNA polymerase II (Pol II) and TFIIF to Scaffold. The cooperative action of hnRNP R and Mediator is diminished by the cyclin-dependent kinase 8 (CDK8) module, which is comprised of CDK8, Cyclin C, MED12 and MED13 of the Mediator subunits. Interestingly, we find that the length of the G-free cassettes, and thereby their transcripts, influences the hnRNP R-mediated facilitation of reinitiation. Indeed, indicative of a possible role of the transcript in facilitating transcription reinitiation, 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. Mutational analyses of hnRNP R indicate that facilitation of initiation and reinitiation requires distinct domains of hnRNP R. Knockdown of hnRNP R in mouse cells compromised rapid induction of the c-fos gene but did not affect transcription of constitutive genes. Together, these results suggest an important role for hnRNP R in regulating robust response of the c-fos gene.
authors: Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. fukudaa@md.tsukuba.ac.jp
authors: Aya
authors: A
authors: Fukuda
authors: Miho
authors: M
authors: Shimada
authors: Tomoyoshi
authors: T
authors: Nakadai
authors: Ken
authors: K
authors: Nishimura
authors: Koji
authors: K
authors: Hisatake
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D056745:Cyclin C / Q000378:metabolism; D056850:Cyclin-Dependent Kinase 8 / Q000378:metabolism; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000378:metabolism; D061785:Transcription Initiation, Genetic
chemical_list: D002352:Carrier Proteins; D056745:Cyclin C; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C486686:Hnrpr protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D035181:TATA-Box Binding Protein; D035581:Transcription Factor TFIIB; D056850:Cyclin-Dependent Kinase 8
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