Dynamic remodelling of human 7SK snRNP controls the nuclear level of active P-TEFb

EMBO J. 2007 Aug 8;26(15):3570-80. doi: 10.1038/sj.emboj.7601783. Epub 2007 Jul 5.


The 7SK small nuclear RNA (snRNA) regulates RNA polymerase II transcription elongation by controlling the protein kinase activity of the positive transcription elongation factor b (P-TEFb). In cooperation with HEXIM1, the 7SK snRNA sequesters P-TEFb into the kinase-inactive 7SK/HEXIM1/P-TEFb small nuclear ribonucleoprotein (snRNP), and thereby, controls the nuclear level of active P-TEFb. Here, we report that a fraction of HeLa 7SK snRNA that is not involved in 7SK/HEXIM1/P-TEFb formation, specifically interacts with RNA helicase A (RHA), heterogeneous nuclear ribonucleoprotein A1 (hnRNP), A2/B1, R and Q proteins. Inhibition of cellular transcription induces disassembly of 7SK/HEXIM1/P-TEFb and at the same time, increases the level of 7SK snRNPs containing RHA, hnRNP A1, A2/B1, R and Q. Removal of transcription inhibitors restores the original levels of the 7SK/HEXIM1/P-TEFb and '7SK/hnRNP' complexes. 7SK/HEXIM1/P-TEFb snRNPs containing mutant 7SK RNAs lacking the capacity for binding hnRNP A1, A2, R and Q are resistant to stress-induced disassembly, indicating that recruitment of the novel 7SK snRNP proteins is essential for disruption of 7SK/HEXIM1/P-TEFb. Thus, we propose that the nuclear level of active P-TEFb is controlled by dynamic and reversible remodelling of 7SK snRNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Nucleus / metabolism*
  • Chromatography, Affinity
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Positive Transcriptional Elongation Factor B / metabolism*
  • Protein Binding
  • RNA / chemistry
  • RNA / metabolism*
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / isolation & purification
  • Ribonucleoproteins, Small Nuclear / metabolism*


  • Ribonucleoproteins, Small Nuclear
  • RNA
  • Positive Transcriptional Elongation Factor B