TAR-Independent Activation of HIV-1 Requires the Activation Domain but Not the RNA-Binding Domain of Tat

The Tat protein of HIV-1 is a potent activator of transcription directed by the viral long terminal repeat. In most cell types this activation requires a specific interaction between Tat and an RNA target termed TAR in the 5′-leader sequence of HIV-1 mRNAs. We have previously reported that in astrocytic cells Tat is capable of activating transcription in a TAR-independent manner through an alternative Tat-responsive element in the LTR (J. P. Taylor et al., EMBO J. 11(9), 3395-3403, 1992). In this report we demonstrate that TAR-independent activation by Tat can effectively bypass competition by decoy TAR RNA molecules. Studies with site-directed mutants demonstrate that the RNA-binding domain of Tat is dispensable for TAR-independent activation of HIV-1. In contrast, the requirement for specific components of the Tat activation domain suggests that common targets exist for this viral trans-activator to exert its activity in TAR-independent and TAR-dependent transactivation pathways of HIV-1 transcriptional activation.