HIV-1 transactivation response element (TAR)

The HIV-1 transactivation response element (TAR) is a highly conserved, 59-nucleotide RNA stem-loop structure located at the 5' end of all nascent HIV-1 transcripts (Karn & Stoltzfus, 2012, Cold Spring Harb Perspect Med). It serves as the primary binding site for the viral transactivator protein, Tat, which is essential for high-level viral gene expression. Upon binding to TAR, Tat recruits the host cell's positive transcription elongation factor b (P-TEFb) complex, composed of Cyclin T1 and CDK9 (Bannwarth & Gatignol, 2005, Nucleic Acids Res). This recruitment triggers the phosphorylation of the C-terminal domain of RNA polymerase II, significantly increasing the efficiency of transcriptional elongation from the HIV-1 long terminal repeat (LTR) promoter. Because the Tat-TAR interaction is critical for viral replication and has no direct human analog, it is a prominent target for the development of novel antiretroviral therapies (Mousseau & Valente, 2012, Pharmaceuticals). Small molecules, aminoglycosides like neomycin, and peptidomimetics designed to bind TAR aim to competitively inhibit Tat binding, thereby suppressing viral production and potentially addressing latent HIV reservoirs (Zapp et al., 1993, Nature; Davidson et al., 2009, J Am Chem Soc).

Other names

TAR RNAHIV-1 TARTrans-activation response elementHIV-1 trans-activation response element

Inhibition of the Tat-TAR interaction to prevent the recruitment of the host P-TEFb complex, thereby blocking the elongation of HIV-1 viral transcripts and suppressing viral replication.