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Molecular and Cellular Biology, January 2006, p. 630-642, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.630-642.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Regulation of Polymerase II Transcription by 7SK snRNA: Two Distinct RNA Elements Direct P-TEFb and HEXIM1 Binding

Laboratoire de Biologie Moléculaire Eucaryote du CNRS, UMR5099 and Université Paul Sabatier, IFR109, 118 route de Narbonne, 31062 Toulouse Cedex 4, France,¹ Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary²

Received 29 September 2005/ Accepted 17 October 2005

The positive transcription elongation factor b (P-TEFb), a complex of Cdk9 and cyclin T1/T2, stimulates transcription by phosphorylating RNA polymerase II. The 7SK small nuclear RNA, in cooperation with HEXIM1 protein, functions as a general polymerase II transcription regulator by sequestering P-TEFb into a large kinase-inactive 7SK/HEXIM1/P-TEFb complex. Here, determination and characterization of the functionally essential elements of human 7SK snRNA directing HEXIM1 and P-TEFb binding led to a new model for the assembly of the 7SK/HEXIM1/P-TEFb regulatory complex. We demonstrate that two structurally and functionally distinct protein binding elements located in the 5'- and 3'-terminal hairpins of 7SK support the in vivo recruitment of HEXIM1 and P-TEFb. Consistently, a minimal regulatory RNA composed of the 5' and 3' hairpins of 7SK can modulate polymerase II transcription in HeLa cells. HEXIM1 binds independently and specifically to the G24-C48/G60-C87 distal segment of the 5' hairpin of 7SK. Binding of HEXIM1 is a prerequisite for association of P-TEFb with the G302-C324 apical region of the 3' hairpin of 7SK that is highly reminiscent of the human immunodeficiency virus transactivation-responsive RNA.

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