Regulation of gene expression by the tat-responsive region of HIV- 1 : role for RNA-protein interactions

The 5$ sp prime$ untranslated region of human immunodeficiency virus type 1 (HIV-1) mRNAs comprises the cis-acting target sequence TAR responsive to the viral transactivator protein Tat. The TAR sequence folds into a stable stem and loop structure and interacts with two proteins: Tat and the cellular double-stranded RNA dependent protein kinase P68. The Tat-TAR interaction is centered on a tri-nucleotide bulge in the RNA. It is thought to bring Tat in proximity to the transcription complex and augment, in an ill-defined manner, the processivity of the RNA polymerase. The P68-TAR interaction is dependent on the integrity of the RNA stem structure and correlates with activation of P68, ultimately leading to inhibition of protein synthesis. However, productive infection by HIV-1 is associated with a decrease in the amount of P68. Downregulation of P68 kinase could provide a means for the virus to switch from latent to active replication. These results demonstrate that the stem and loop structure in TAR has both positive and negative effects on viral gene expression