MCB Accepts, published online ahead of print on 20 August 2007

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Mol. Cell. Biol. doi:10.1128/MCB.00975-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

Charlotte BARRANDON, François BONNET, Van Trung NGUYEN, Valérie LABAS, and Olivier BENSAUDE^*

UMR 8541 CNRS, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 PARIS Cedex 05, UMR 7637 CNRS, Ecole Supérieure de Physique et Chimie Industrielles, 75005 PARIS, France

^* To whom correspondence should be addressed. Email: bensaude{at}ens.fr.

The positive transcription elongation factor (P-TEFb) controls elongation of transcription by RNA polymerase II. P-TEFb is inactivated upon binding to HEXIM1 or HEXIM2 proteins associated to a non-coding RNA, the 7SK. In response to inhibition of transcription, 7SK RNA as well as HEXIM proteins are released by an unknown mechanism and P-TEFb is activated. New partners of 7SK RNA were searched as potential players in this feed-back process. A subset of heterogeneous ribonuclear proteins, hnRNP Q & R and hnRNP A1 & A2, were thus identified as major 7SK RNA-associated proteins. Association of 7SK RNA to these hnRNPs increased when P-TEFb.HEXIM1.7SK was dissociated following inhibition of transcription or HEXIM1 knock-down. 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 hnRNP A1 and A2 were knocked-down by siRNA. As hnRNPs are known to interact transiently with RNA while it is synthesized, hnRNPs released from nascent transcripts might trap 7SK RNA and thereby contribute to activate P-TEFb.

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