Poly(ADP-ribose) Polymerase-1 Is a Negative Regulator of HIV-1 Transcription through Competitive Binding to TAR RNA with TatPositive Transcription Elongation Factor b (p-TEFb) Complex.

Human immunodeficiency virus, type 1 (HIV-1) transcription is regulated by a virus-encoded protein, Tat, which forms a complex with a host cellular factor, positive transcription elongation factor b (P-TEFb). When this complex binds to TAR RNA synthesized from the HIV-1 long terminal repeat promoter element, transcription is trans-activated. In this study we showed that, in host cells, HIV-1 transcription is negatively regulated by competition of poly(ADP-ribose) polymerase-1 (PARP-1) with Tat·P-TEFb for binding to TAR RNA. PARP-1, which has a high affinity for TAR RNA (KD = 1.35 × 10-10 M), binds to the loop region of TAR RNA and displaces Tat or Tat·P-TEFb from the RNA. In vitro transcription assays showed that this displacement leads to suppression of Tat-mediated trans-activation of transcription. Furthermore in vivo expression of luciferase or destabilized enhanced green fluorescent protein genes under the control of the HIV-1 long terminal repeat promoter was suppressed by PARP-1. Thus, these results suggest that PARP-1 acts as a negative regulator of HIV-1 transcription through competitive binding with Tat or the Tat·P-TEFb complex to TAR RNA. [ABSTRACT FROM AUTHOR]