description
The Tat protein is a viral transactivator protein that regulates HIV-1 gene expression by controlling RNA Pol II-mediated elongation (reviewed in Karn 1999; Taube et al. 1999; Liou et al. 2004; Barboric and Peterlin 2005). Tat appears to be required in order to overcome the arrest of RNA Pol II by the negative transcriptional elongation factors DSIF and NELF (Wada et al. 1998; Yamaguchi et al. 1999; Yamaguchi et al 2002; Fujinaga et al. 2004). While Pol II can associate with the proviral LTR and initiate transcription in the absence of Tat, these polymerase complexes are non-processive and dissociate from the template prematurely producing very short transcripts (Kao et al. 1987). Tat associates with the RNA element, TAR, which forms a stem loop structure in the leader RNA sequence (Dingwall et al. 1989). Tat also associates with the cellular kinase complex P-TEFb(Cyclin T1:Cdk9) and recruits it to the TAR stem loop structure (Herrmann, 1995) (Wei et al. 1998). This association between Tat, TAR and P-TEFb(Cyclin T1:Cdk9) is believed to bring the catalytic subunit of this kinase complex (Cdk9) in close proximity to Pol II where it hyperphosphorylates the CTD of RNA Pol II (Zhou et al. 2000). The RD subunits of NELF and the SPT5 subunit of DSIF, which associate through RD with the bottom stem of TAR, are also phosphorylated by P-TEFb(Cyclin T1:Cdk9) (Yamaguchi et al. 2002; Fujinaga et al. 2004; Ivanov et al. 2000). Phosphorylation of RD results in its dissociation from TAR. Thus, Tat appears to facilitate transcriptional elongation of the HIV-1 transcript by hyperphosphorylating the RNA Poll II CTD and by removing the negative transcription elongation factors from TAR. In addition, there is evidence that the association of Tat with P-TEFb(Cyclin T1:Cdk9) alters the substrate specificity of P-TEFb enhancing phosphorylation of ser5 residues in the CTD of RNA Pol II (Zhou et al. 2000)

external resources
NCBI:1269076
REACTOME:R-HSA-167246
PUBMED:2825027
PUBMED:9450929
PUBMED:11940650
PUBMED:2476805
PUBMED:10866664
PUBMED:10757782
PUBMED:10550206
PUBMED:10199401
PUBMED:15719065
PUBMED:10562489
PUBMED:15183343
PUBMED:14701750
PUBMED:7853496
PUBMED:9491887

genes
CCNH , CCNT1 , CDK7 , CDK9 , ERCC2 , ERCC3 , GTF2F1 , GTF2F2 , GTF2H1 , GTF2H2 , GTF2H3 , GTF2H4 , MNAT1 , NCBP1 , POLR2A , POLR2B , POLR2C , POLR2D , POLR2E , POLR2F , POLR2G , POLR2H , POLR2I , POLR2J , POLR2K , POLR2L , SSRP1 , SUPT4H1 , SUPT5H , TCEA1 , ELOC , ELOB , ELOA , NELFA , NELFE , ELL , CTDP1 , SUPT16H , NCBP2 , NELFB , ELOA2 , NELFCD , ELOA3 , GTF2H5 , ELOA3B , MIR943 , MIR1236 , MIR2861 , ELOA3D , MIR3960 ,