Coordination of transcription, RNA processing, and surveillance by P-TEFb kinase on heat shock genes

Mol Cell. 2004 Jan 16;13(1):55-65. doi: 10.1016/s1097-2765(03)00526-4.


Positive transcription elongation factor b (P-TEFb) is a kinase that phosphorylates the carboxyl-terminal domain (CTD) of RNA Polymerase II (Pol II). Here, we show that flavopiridol, a highly specific P-TEFb kinase inhibitor, dramatically reduces the global levels of Ser2--but not Ser5--phosphorylated CTD at actively transcribed loci on Drosophila polytene chromosomes under both normal and heat shocked conditions. Brief treatment of Drosophila cells with flavopiridol leads to a reduction in the accumulation of induced hsp70 and hsp26 RNAs. Surprisingly, the density of transcribing Pol II and Pol II progression through hsp70 in vivo are nearly normal in flavopiridol-treated cells. The major defect in expression is at the level of 3' end processing. A similar but more modest 3' processing defect was also observed for hsp26. We propose that P-TEFb phosphorylation of Pol II CTD coordinates transcription elongation with 3' end processing, and failure to do so leads to rapid RNA degradation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Hot Temperature
  • Models, Genetic
  • Phosphorylation
  • Piperidines / pharmacology
  • Positive Transcriptional Elongation Factor B / metabolism*
  • Protein Structure, Tertiary
  • RNA / analysis
  • RNA / drug effects
  • RNA / metabolism
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA, Small Interfering / metabolism
  • Serine / drug effects
  • Transcription, Genetic*


  • Drosophila Proteins
  • Enzyme Inhibitors
  • Flavonoids
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Piperidines
  • RNA, Small Interfering
  • Serine
  • alvocidib
  • RNA
  • Positive Transcriptional Elongation Factor B
  • RNA Polymerase II