Trans-activation response element RNA (TAR RNA)

The Trans-activation response element RNA (TAR RNA) is a stem-loop structure present at the 5′ ends of HIV-1 transcripts. It is central for HIV-1 transcriptional activation; binding of the viral Tat protein to TAR recruits host transcriptional machinery (notably P-TEFb, a complex of Cyclin T1 and CDK9), resulting in enhanced elongation of viral RNA by RNA polymerase II[4][2][3][5][9]. TAR RNA functions in multiple stages of the HIV life cycle: reverse transcription, transcription, genome dimerization, packaging, and modulation of innate immune responses via inhibition of PKR[2]. It also acts as a precursor to viral microRNAs that protect infected cells from apoptosis[4]. Inhibiting the Tat-TAR interaction is a major focus in HIV drug development, but no clinical drugs specifically target TAR directly[2][4]. TAR is dynamic, with both the upper stem (major Tat-binding site) and lower stem (PKR interaction) required for optimal viral replication[2]. Its function is structurally dependent: loss or mutation of critical bulges/loops impairs Tat binding and viral transcription[1][6][5]. The TAR element also serves as an enhancer for transcriptional processivity and acts as a switch for viral gene expression[7].

Other names

HIV-1 TARTAR elementTransactivation response element

Tat inhibitors prevent Tat-TAR binding, disrupting HIV transcriptional elongation. PKR activators could overcome TAR's suppression of innate immunity.