RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation.
The transition from transcription initiation to elongation at the HIV-1 promoter is controlled by Tat, which recruits P-TEFb to TAR RNA to phosphorylate RNA polymerase II. It has long been unclear why the HIV-1 promoter is incompetent for elongation. We report that P-TEFb is recruited to the promoter in a catalytically inactive state bound to the inhibitory 7SK small nuclear ribonucleoprotein (snRNP), thereby preventing elongation. It also has long been believed that TAR functions to recruit Tat to the promoter, but we find that Tat is recruited to the DNA template before TAR is synthesized. We propose that TAR binds Tat and P-TEFb as it emerges on the nascent transcript, competitively displacing the inhibitory 7SK snRNP and activating the P-TEFb kinase. Recruitment of an inhibitory snRNP complex at an early stage in the transcription cycle provides a new paradigm for controlling gene expression with a noncoding RNA.
D'Orso
Iván
I
Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA.
Frankel
Alan D
AD
D004257:DNA Polymerase II / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D017411:Ribonucleoproteins, Small Nuclear; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D042925:Positive Transcriptional Elongation Factor B; D004257:DNA Polymerase II