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

The transcription of eukaryotic protein-coding genes involves complex regul ation of RNA polymerase (Pol) II activity in response to physiological cond itions and developmental cues. One element of this regulation involves phos phorylation of the carboxy-terminal domain (CTD) of the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the k inase 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 un known function(2,3). P-TEFb and 7SK associate in a specific and reversible manner. In contrast to the smaller P-TEFb complexes, which have a high kina se activity, the larger 7SK/P-TEFb complexes show very weak kinase activity . Inhibition of cellular transcription by chemical agents or ultraviolet ir radiation trigger the complete disruption of the P-TEFb/7SK complex, and en hance 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.