The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes

EMBO Rep. 2008 Jun;9(6):569-75. doi: 10.1038/embor.2008.72. Epub 2008 May 16.

Abstract

The positive transcription elongation factor b (P-TEFb) is a heterodimeric complex composed of cyclin-dependent kinase 9 and its regulator cyclin T1/2. It stimulates transcription elongation by phosphorylation of serine 2 residues in the carboxy-terminal domain of polymerase II. 7SK RNA and HEXIM proteins can antagonize transcriptional stimulation by sequestering P-TEFb in a catalytically inactive ribonucleoprotein (RNP). Here, we show that the previously uncharacterized La-related protein 7 (LARP7) has a role in 7SK-mediated regulation of transcription. LARP7 binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA and is an integral part of the 7SK RNP. On stimulation, LARP7 remains associated with 7SK RNA, whereas P-TEFb is released. Interestingly, reduction of LARP7 by RNA interference enhances transcription from cellular polymerase II promoters, as well as a TAT-dependent HIV-1 promoter. Thus, LARP7 is a negative transcriptional regulator of polymerase II genes, acting by means of the 7SK RNP system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Gene Expression Regulation*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Nucleic Acid Conformation
  • Positive Transcriptional Elongation Factor B / genetics
  • Positive Transcriptional Elongation Factor B / metabolism
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / chemistry
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Transcription Factors
  • Transcription, Genetic*
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • Autoantigens
  • HEXIM1 protein, human
  • Larp7 protein, human
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • SS-B antigen
  • Transcription Factors
  • Viral Proteins
  • Positive Transcriptional Elongation Factor B
  • RNA Polymerase II