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

Nature. 2001 Nov 15;414(6861):322-5. doi: 10.1038/35104581.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cyclin T
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / antagonists & inhibitors*
  • Cyclins / metabolism
  • DNA, Viral
  • Enzyme Inhibitors
  • Gene Expression Regulation
  • HIV / genetics
  • HeLa Cells
  • Humans
  • Positive Transcriptional Elongation Factor B
  • Promoter Regions, Genetic
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Polymerase II / metabolism
  • RNA, Small Nuclear / metabolism*

Substances

  • CCNT1 protein, human
  • CCNT2 protein, human
  • Cyclin T
  • Cyclins
  • DNA, Viral
  • Enzyme Inhibitors
  • RNA, Small Nuclear
  • Protein Kinases
  • carboxy-terminal domain kinase
  • Positive Transcriptional Elongation Factor B
  • Protein-Serine-Threonine Kinases
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases
  • RNA Polymerase II