HIV-1 trans-activation response element (TAR)

The HIV-1 trans-activation response (TAR) element is a critical 59-nucleotide RNA stem-loop structure located at the 5' end of all nascent viral transcripts. Its primary biological function is to serve as a binding site for the viral trans-activator protein Tat, which subsequently recruits the host positive transcription elongation factor b (P-TEFb) complex, containing CDK9 and Cyclin T1, to the viral promoter. This interaction is indispensable for the efficient transition of RNA polymerase II from a paused state to productive elongation; without it, the virus produces only short, non-functional transcripts, effectively stalling viral replication. Because of its high sequence conservation and essential role in the viral life cycle, TAR is considered a significant therapeutic target for anti-HIV drug discovery. Beyond its role in transcription, the TAR element acts as a pre-microRNA that is processed into viral miRNAs which may downregulate host pro-apoptotic genes to promote the survival of infected cells. Experimental therapeutic approaches focus on small molecules, peptidomimetics, and cyclic peptides designed to competitively block the Tat-TAR interface, although achieving clinical-grade selectivity and potency remains a major challenge.

Other names

TAR RNAHIV-1 TARTrans-activation responsive elementTransactivating response elementTAR hairpinmir-TAR

Competitive inhibition of the viral Tat protein's binding to the TAR RNA bulge and apical loop, thereby preventing the recruitment of the P-TEFb complex and disrupting the transcriptional elongation of the HIV-1 genome [1, 2, 4, 8, 27].