Tat gets the "green" light on transcription initiation.
Human immunodeficiency virus type 1 (HIV-1) Tat transactivation is an essential step in the viral life cycle. Over the past several years, it has become widely accepted that Tat exerts its transcriptional effect by binding the transactivation-responsive region (TAR) and enhancing transcriptional elongation. Consistent with this hypothesis, it has been shown that Tat promotes the binding of P-TEFb, a transcription elongation factor composed of cyclin T1 and cdk9, and the interaction of Tat with P-TEFb and TAR leads to hyperphosphorylation of the C-terminal domain (CTD) of RNA Pol II and increased processivity of RNA Pol II. A recent report, however, has generated renewed interest that Tat may also play a critical role in transcription complex (TC) assembly at the preinitiation step. Using in vivo chromatin immunoprecipitation assays, the authors reported that the HIV TC contains TBP but not TBP-associated factors. The stimulatory effect involved the direct interaction of Tat and P-TEFb and was evident at the earliest step of TC assembly, the TBP-TATA box interaction. In this article, we will review this data in context of earlier data which also support Tat's involvement in transcriptional complex assembly. Specifically, we will discuss experiments which demonstrated that Tat interacted with TBP and increased transcription initiation complex stability in cell free assays. We will also discuss studies which demonstrated that over expression of TBP alone was sufficient to obtain Tat activated transcription in vitro and in vivo. Finally, studies using self-cleaving ribozymes which suggested that Tat transactivation was not compatible with pausing of the RNA Pol II at the TAR site will be discussed.
Brady
John
J
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892, USA. bradyj@dce41.nci.nih.gov
Kashanchi
Fatah
F
D017500:Adenovirus E1A Proteins / Q000502:physiology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D002843:Chromatin / Q000737:chemistry; D015696:Gene Products, tat / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D017405:Herpes Simplex Virus Protein Vmw65 / Q000502:physiology; D006801:Humans; D016601:RNA-Binding Proteins / Q000502:physiology; D035181:TATA-Box Binding Protein / Q000502:physiology; D035362:Transcription Factor TFIID / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099253:Trans-Activation Responsive RNA-Binding Protein
D017500:Adenovirus E1A Proteins; D000952:Antigens, Polyomavirus Transforming; D002843:Chromatin; D015696:Gene Products, tat; D017405:Herpes Simplex Virus Protein Vmw65; D016601:RNA-Binding Proteins; D035181:TATA-Box Binding Protein; D035362:Transcription Factor TFIID; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099253:Trans-Activation Responsive RNA-Binding Protein