The study of the regulation of human immunodeficiency virus type 1 (HIV-1) gene expression has increased our understanding of the biology of complex retroviruses and provided useful insights into eukaryotic transcriptional control. The HIV-1 viral protein Tat increases HIV-1 transcription more than 100-fold and is absolutely required for viral replication (Dayton et al, 1986; Fisher et al, 1986). Tat is a protein of 86 amino acids that functions by binding to an RNA element designated TAR (for trans-activation response element) (reviewed in Gait and Karn, 1993; Cullen, 1995). TAR is a highly structured RNA element located at the 5' end of all HIV-1 transcripts and is composed of double-stranded stems, a four-nucleotide bulge, and a six-nucleotide loop (Fig. 1: TAR). Tat binds specifically to the TAR bulge in vitro and on binding alters the structure of the TAR RNA (Colvin and Garcia-Blanco, 1992; Puglisi et al, 1992). Although the structure of TAR and the requirements for Tat-TAR binding have been thoroughly investigated, little is known about the mechanism by which Tat increases HIV-1 transcription. Current models suggest a role for Tat in the regulation of transcriptional initiation as well as elongation (reviewed in Cullen, 1993; Jones and Peterlin, 1994; Kam et al, 1996).
mRNA Formation and Function
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