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
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Research Support, Non-U.S. Gov't
MeSH terms
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Autoantigens / genetics
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Autoantigens / metabolism*
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Gene Expression Regulation*
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HIV-1 / genetics
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HIV-1 / metabolism
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HeLa Cells
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Humans
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Nucleic Acid Conformation
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Positive Transcriptional Elongation Factor B / genetics
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Positive Transcriptional Elongation Factor B / metabolism
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Promoter Regions, Genetic
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RNA Interference
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RNA Polymerase II / genetics*
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RNA Polymerase II / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Ribonucleoproteins / chemistry
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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SS-B Antigen
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Transcription Factors
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Transcription, Genetic*
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Viral Proteins / genetics*
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Viral Proteins / metabolism
Substances
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Autoantigens
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HEXIM1 protein, human
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Larp7 protein, human
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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Ribonucleoproteins
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Transcription Factors
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Viral Proteins
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Positive Transcriptional Elongation Factor B
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RNA Polymerase II