HIV trans-activation and transcription control mechanisms

Promoter-specific transcription factors, whose function was once thought to be limited to initiation, are now known to have more diverse roles in RNA metabolism, including the cellular localization of transcripts and the integration of RNA initiation with attenuation and RNA 3' end formation. The human immunodeficiency viruses (HIV-1 and HIV-2) provide a useful system to study such proteins, since distinct DNA and RNA elements downstream of the site of transcription initiation act in conjunction with the promoter to regulate the induction and attenuation of RNA synthesis. Sequences corresponding to the 5' untranslated leader of HIV-1 and HIV-2 harbor at least three distinct elements: (i) a DNA domain that binds LBP-1, a cellular activator of initiation; (ii) a structured RNA element critical for the function of the HIV-1 trans-activating protein, Tat; and (iii) an RNA element required for the production of attenuated RNAs from the basal (uninduced) promoter. These attenuated leader RNAs seem to be created in vitro by stalled RNA polymerase II complexes that may be uniquely capable of rapidly processing RNA. Tat-mediated increases in steady-state levels of viral transcripts appear from nuclear run-on experiments to involve a control mechanism at both initiation and early post-initiation steps. Studies that implicate a role for Tat in post-transcriptional control suggest the existence of a mechanism for the coordination of eukaryotic transcription and translation, possibly through the assembly of nuclear regulatory factors at the 5' end of the RNA.