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PMID: 17709395 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The transcription-dependent dissociation of P-TEFb-HEXIM1-7SK RNA relies upon formation of hnRNP-7SK RNA complexes.

Molecular and cellular biology ·Vol. 27 ·No. 20 ·2007-10-00 ·Pages 6996-7006

Barrandon C, Bonnet F, Nguyen VT, Labas V, Bensaude O

Abstract

The positive transcription elongation factor P-TEFb controls the elongation of transcription by RNA polymerase II. P-TEFb is inactivated upon binding to HEXIM1 or HEXIM2 proteins associated with a noncoding RNA, 7SK. In response to the inhibition of transcription, 7SK RNA, as well as HEXIM proteins, is released by an unknown mechanism and P-TEFb is activated. New partners of 7SK RNA were searched for as potential players in this feedback process. A subset of heterogeneous ribonuclear proteins, hnRNPs Q and R and hnRNPs A1 and A2, were thus identified as major 7SK RNA-associated proteins. The degree of association of 7SK RNA with these hnRNPs increased when P-TEFb-HEXIM1-7SK was dissociated following the inhibition of transcription or HEXIM1 knockdown. This finding suggested that 7SK RNA shuttles from HEXIM1-P-TEFb complexes to hnRNPs. The transcription-dependent dissociation of P-TEFb-HEXIM1-7SK complexes was attenuated when both hnRNPs A1 and A2 were knocked down by small interfering RNA. As hnRNPs are known to interact transiently with RNA while it is synthesized, hnRNPs released from nascent transcripts may trap 7SK RNA and thereby contribute to the activation of P-TEFb.

MeSH Terms
HeLa Cells Heterogeneous-Nuclear Ribonucleoproteins/genetics,metabolism Humans Macromolecular Substances/metabolism Models, Genetic Positive Transcriptional Elongation Factor B/genetics,metabolism Protein Isoforms/genetics,metabolism RNA Interference RNA, Small Cytoplasmic/genetics,metabolism RNA-Binding Proteins/genetics,metabolism Signal Recognition Particle/genetics,metabolism Transcription Factors Transcription, Genetic
Chemicals
7SL RNA HEXIM1 protein, human Heterogeneous-Nuclear Ribonucleoproteins Macromolecular Substances Protein Isoforms RNA, Small Cytoplasmic RNA-Binding Proteins Signal Recognition Particle Transcription Factors Positive Transcriptional Elongation Factor B
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Barrandon Charlotte
UMR 8541 CNRS, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
Bonnet François
Nguyen Van Trung
Labas Valérie
Bensaude Olivier
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.00975-07
Published
2007-10-00
Epub
2007-00-20
Pages
6996-7006
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2168891
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.00975-07 PMC Full Text View journal details
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