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7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes

Nature volume 414, pages 322–325 (2001)Cite this article

Abstract

The transcription of eukaryotic protein-coding genes involves complex regulation of RNA polymerase (Pol) II activity in response to physiological conditions and developmental cues. One element of this regulation involves phosphorylation of the carboxy-terminal domain (CTD) of the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the kinase CDK9 and cyclin T1 or T2 (ref. 1). Here we report that in human HeLa cells more than half of the P-TEFb is sequestered in larger complexes that also contain 7SK RNA, an abundant, small nuclear RNA (snRNA) of hitherto unknown function2,3. P-TEFb and 7SK associate in a specific and reversible manner. In contrast to the smaller P-TEFb complexes, which have a high kinase activity, the larger 7SK/P-TEFb complexes show very weak kinase activity. Inhibition of cellular transcription by chemical agents or ultraviolet irradiation trigger the complete disruption of the P-TEFb/7SK complex, and enhance CDK9 activity. The transcription-dependent interaction of P-TEFb with 7SK may therefore contribute to an important feedback loop modulating the activity of RNA Pol II.

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Figure 1: Structural and functional characterization of human CDK9, cyclin T1 and cyclin T2 complexes.
Figure 2: The large complexes of CDK9/cyclin T1 or T2 contain 7SK.
Figure 3: Transcription inhibition promotes disruption of the 7SK/CDK9/cyclin T complexes.

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Acknowledgements

This research was supported by grants from the Agence Nationale de Recherche sur le Sida, Association pour la Recherche sur le Cancer, the Ligue Nationale Contre le Cancer (Comité de Paris), the France-Berkeley fund and a Federation of European Biochemical Societies fellowship to A.A.M. We thank P. Ascher, M.-F. Dubois, D. H. Price and all members of the Groupe de Biologie Cellulaire de la Transcription for help and discussions, and Z. Yang and Q. Zhou for communicating their work before publication and providing the G3H cells.

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Authors and Affiliations

  1. Génétique Moléculaire, UMR 8541 CNRS, Ecole Normale Supérieure, 46 rue d’Ulm, Paris, 75230 cedex 05, France

    Van Trung Nguyen, Annemieke A. Michels & Olivier Bensaude

  2. Laboratoire de Biologie Moléculaire Eucaryote du CNRS, Université Paul Sabatier, 118 route de Narbonne, Toulouse, 31062, France

    Tamás Kiss

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  1. Van Trung Nguyen
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Correspondence to Olivier Bensaude.

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Nguyen, V., Kiss, T., Michels, A. et al. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414, 322–325 (2001). https://doi.org/10.1038/35104581

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