RRC ID 44607
Author Fukuda A, Shimada M, Nakadai T, Nishimura K, Hisatake K.
Title Heterogeneous nuclear ribonucleoprotein R cooperates with mediator to facilitate transcription reinitiation on the c-Fos gene.
Journal PLoS One
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.
Volume 8(8)
Pages e72496
Published 2013-1-1
DOI 10.1371/journal.pone.0072496
PII PONE-D-12-25470
PMID 23967313
PMC PMC3742609
MeSH Animals Carrier Proteins / metabolism* Cell Line Cyclin C / metabolism Cyclin-Dependent Kinase 8 / metabolism Gene Expression Regulation Heterogeneous-Nuclear Ribonucleoproteins / chemistry Heterogeneous-Nuclear Ribonucleoproteins / metabolism* Mice Promoter Regions, Genetic Protein Binding Protein Interaction Domains and Motifs Proto-Oncogene Proteins c-fos / genetics* TATA-Box Binding Protein / metabolism Transcription Factor TFIIB / metabolism Transcription Initiation, Genetic*
IF 2.74
Times Cited 5
Human and Animal Cells 10T1/2(RCB0247)