7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes.
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 function. 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.
Nguyen
V T
VT
Génétique Moléculaire, UMR 8541 CNRS, Ecole Normale Supérieure, 46 rue d'Ulm, 75230 Paris cedex 05, France.
Kiss
T
T
Michels
A A
AA
Bensaude
O
O
D001665:Binding Sites; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D005786:Gene Expression Regulation; D006678:HIV / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D042925:Positive Transcriptional Elongation Factor B; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism*
C503684:CCNT1 protein, human; C441622:CCNT2 protein, human; D056906:Cyclin T; D016213:Cyclins; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D012342:RNA, Small Nuclear; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II