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Article
Subject Categories: Chromatin & Transcription | RNA
The EMBO Journal (2007) 26, 3570–3580, doi:10.1038/sj.emboj.7601783
Published online 5 July 2007
Dynamic remodelling of human 7SK snRNP controls the nuclear level of active P-TEFb
Elodie Van Herreweghe1, Sylvain Egloff1, Isabelle Goiffon1, Beáta E Jády1, Carine Froment2, Bernard Monsarrat2 and Tamás Kiss1, 3
1 Laboratoire de Biologie Moléculaire Eucaryote, UMR5099, CNRS-Université Paul Sabatier, Toulouse, France
2 Plate-forme protéomique, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, Toulouse, France
3 Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary

To whom correspondence should be addressed
Tamás Kiss, Laboratoire de Biologie Moléculaire Eucaryote, UMR5099, CNRS-Université Paul Sabatier, IFR109, 118 route de Narbonne, Toulouse Cedex 9, 31062, France. Tel.: +33 561 335 907; Fax: +33 561 335 886; E-mail: tamas@ibcg.biotoul.fr

Received 12 March 2007; Accepted 11 June 2007; Published online 5 July 2007.
Abstract
The 7SK small nuclear RNA (snRNA) regulates RNA polymerase II transcription elongation by controlling the protein kinase activity of the positive transcription elongation factor b (P-TEFb). In cooperation with HEXIM1, the 7SK snRNA sequesters P-TEFb into the kinase-inactive 7SK/HEXIM1/P-TEFb small nuclear ribonucleoprotein (snRNP), and thereby, controls the nuclear level of active P-TEFb. Here, we report that a fraction of HeLa 7SK snRNA that is not involved in 7SK/HEXIM1/P-TEFb formation, specifically interacts with RNA helicase A (RHA), heterogeneous nuclear ribonucleoprotein A1 (hnRNP), A2/B1, R and Q proteins. Inhibition of cellular transcription induces disassembly of 7SK/HEXIM1/P-TEFb and at the same time, increases the level of 7SK snRNPs containing RHA, hnRNP A1, A2/B1, R and Q. Removal of transcription inhibitors restores the original levels of the 7SK/HEXIM1/P-TEFb and '7SK/hnRNP' complexes. 7SK/HEXIM1/P-TEFb snRNPs containing mutant 7SK RNAs lacking the capacity for binding hnRNP A1, A2, R and Q are resistant to stress-induced disassembly, indicating that recruitment of the novel 7SK snRNP proteins is essential for disruption of 7SK/HEXIM1/P-TEFb. Thus, we propose that the nuclear level of active P-TEFb is controlled by dynamic and reversible remodelling of 7SK snRNP.
Keywords: regulatory RNAs, snRNAs, snRNPs, transcription elongation
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