The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes.
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.
Mesh Terms:
Autoantigens, Gene Expression Regulation, HIV-1, HeLa Cells, Humans, Nucleic Acid Conformation, Positive Transcriptional Elongation Factor B, Promoter Regions, Genetic, RNA Interference, RNA Polymerase II, RNA-Binding Proteins, Recombinant Fusion Proteins, Ribonucleoproteins, Transcription, Genetic, Viral Proteins
Autoantigens, Gene Expression Regulation, HIV-1, HeLa Cells, Humans, Nucleic Acid Conformation, Positive Transcriptional Elongation Factor B, Promoter Regions, Genetic, RNA Interference, RNA Polymerase II, RNA-Binding Proteins, Recombinant Fusion Proteins, Ribonucleoproteins, Transcription, Genetic, Viral Proteins
EMBO Rep.
Date: Jun. 01, 2008
PubMed ID: 18483487
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