PMID- 23967313
OWN - NLM
STAT- MEDLINE
DCOM- 20140514
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Heterogeneous nuclear ribonucleoprotein R cooperates with mediator to facilitate 
      transcription reinitiation on the c-Fos gene.
PG  - e72496
LID - 10.1371/journal.pone.0072496 [doi]
LID - e72496
AB  - 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.
FAU - Fukuda, Aya
AU  - Fukuda A
AD  - Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. 
      fukudaa@md.tsukuba.ac.jp
FAU - Shimada, Miho
AU  - Shimada M
FAU - Nakadai, Tomoyoshi
AU  - Nakadai T
FAU - Nishimura, Ken
AU  - Nishimura K
FAU - Hisatake, Koji
AU  - Hisatake K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130813
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclin C)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoproteins)
RN  - 0 (Hnrpr protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (TATA-Box Binding Protein)
RN  - 0 (Transcription Factor TFIIB)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 8)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*metabolism
MH  - Cell Line
MH  - Cyclin C/metabolism
MH  - Cyclin-Dependent Kinase 8/metabolism
MH  - Gene Expression Regulation
MH  - Heterogeneous-Nuclear Ribonucleoproteins/chemistry/*metabolism
MH  - Mice
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Proto-Oncogene Proteins c-fos/*genetics
MH  - TATA-Box Binding Protein/metabolism
MH  - Transcription Factor TFIIB/metabolism
MH  - *Transcription Initiation, Genetic
PMC - PMC3742609
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/24 06:00
MHDA- 2014/05/16 06:00
PMCR- 2013/08/13
CRDT- 2013/08/23 06:00
PHST- 2012/08/23 00:00 [received]
PHST- 2013/07/15 00:00 [accepted]
PHST- 2013/08/23 06:00 [entrez]
PHST- 2013/08/24 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
PHST- 2013/08/13 00:00 [pmc-release]
AID - PONE-D-12-25470 [pii]
AID - 10.1371/journal.pone.0072496 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 13;8(8):e72496. doi: 10.1371/journal.pone.0072496. eCollection 
      2013.