HIV-1 trans-activation response element RNA (HIV-1 TAR RNA)

The HIV-1 trans-activation response element (TAR) RNA is a highly conserved 59-nucleotide stem-loop structure located at the 5' end of all nascent HIV-1 transcripts (Karn & Stoltzfus, 2012). Its primary biological function is to serve as a binding scaffold for the viral trans-activator protein (Tat) and the host cellular positive transcription elongation factor b (P-TEFb) complex (Bannwarth & Gatignol, 2005). The interaction between Tat and the U-rich bulge of the TAR RNA is critical for the transition of the viral RNA polymerase II from a non-processive to a highly processive state, enabling the full-length transcription of the HIV-1 genome (Mousseau et al., 2015). In the absence of this interaction, transcription terminates prematurely, effectively halting viral replication. As a therapeutic target, TAR RNA is attractive due to its high conservation across different HIV-1 strains and its essential role in the viral life cycle. Experimental drugs targeting TAR RNA, including small molecules and peptidomimetics, aim to sterically hinder Tat binding or induce conformational changes in the RNA that prevent the assembly of the transcription complex (Abulwerdi et al., 2014). However, achieving high specificity for viral RNA over host RNA remains a significant challenge in drug development.

Other names

TAR RNATrans-activation response elementHIV-1 5'-UTR TARHIV-1 TAR stem-loopHIV-1 TAR bulge

Disruption of the Tat-TAR RNA interaction to inhibit transcriptional elongation of the HIV-1 provirus.