LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated

Nucleic Acids Res. 2008 Apr;36(7):2219-29. doi: 10.1093/nar/gkn061. Epub 2008 Feb 16.


Regulation of the elongation phase of RNA polymerase II transcription by P-TEFb is a critical control point for gene expression. The activity of P-TEFb is regulated, in part, by reversible association with one of two HEXIMs and the 7SK snRNP. A recent proteomics survey revealed that P-TEFb and the HEXIMs are tightly connected to two previously-uncharacterized proteins, the methyphosphate capping enzyme, MEPCE, and a La-related protein, LARP7. Glycerol gradient sedimentation analysis of lysates from cells treated with P-TEFb inhibitors, suggested that the 7SK snRNP reorganized such that LARP7 and 7SK remained associated after P-TEFb and HEXIM1 were released. Immunodepletion of LARP7 also depleted most of the 7SK regardless of the presence of P-TEFb, HEXIM or hnRNP A1 in the complex. Small interfering RNA knockdown of LARP7 in human cells decreased the steady-state level of 7SK, led to an initial increase in free P-TEFb and increased Tat transactivation of the HIV-1 LTR. Knockdown of LARP7 or 7SK ultimately caused a decrease in total P-TEFb protein levels. Our studies have identified LARP7 as a 7SK-binding protein and suggest that free P-TEFb levels are determined by a balance between release from the large form and reduction of total P-TEFb.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Gene Products, tat / metabolism
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Humans
  • Positive Transcriptional Elongation Factor B / metabolism*
  • RNA Interference
  • RNA, Small Nuclear / metabolism
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / analysis
  • Ribonucleoproteins / antagonists & inhibitors
  • Ribonucleoproteins / metabolism*
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • Transcription Factors
  • Transcriptional Activation


  • Gene Products, tat
  • HEXIM1 protein, human
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Larp7 protein, human
  • RNA, Small Nuclear
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • Transcription Factors
  • Positive Transcriptional Elongation Factor B