Human immunodeficiency virus type 1 trans-activation response element (TAR RNA)

The Human immunodeficiency virus type 1 trans-activation response (TAR) element 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). Its primary biological function is to serve as a binding site for the viral trans-activator protein (Tat) and the host cellular positive transcription elongation factor b (P-TEFb) complex (Wei et al., 1998, Cell). This interaction is critical for the transition of RNA polymerase II from a non-processive to a highly processive state, enabling the efficient elongation of the viral genome (Zhou & Rana, 2002, Acc Chem Res). In the absence of the Tat-TAR interaction, HIV-1 transcription is extremely inefficient, leading to truncated transcripts and a failure of viral replication (Mousseau et al., 2015, Cell Host Microbe). Consequently, the TAR RNA element is a significant therapeutic target for the development of anti-retroviral drugs aimed at inhibiting viral gene expression (Abulwerdi et al., 2016, J Med Chem). Research efforts focus on small molecules, peptides, and antisense oligonucleotides that can competitively bind to the TAR bulge or loop, thereby disrupting the recruitment of the Tat/P-TEFb complex (Donahue et al., 2017, Chem Biol).

Other names

TARTrans-activation response elementHIV-1 TAR RNA

Competitive inhibition of the Tat protein binding to the TAR RNA bulge, preventing the recruitment of the P-TEFb complex and subsequent transcriptional elongation of the HIV-1 provirus (Karn & Stoltzfus, 2012).