Poly(ADP-ribose) polymerase-1 is a negative regulator of HIV-1 transcription through competitive binding to TAR RNA with Tat.positive 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 (K(D) = 1.35 x 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.
Parent
Marianne
M
Division of Health and Environmental Research, Laval University Medical Center, Ste-Foy, Quebec G1V 4G2, Canada.
Yung
Tetsu M C
TM
Rancourt
Ann
A
Ho
Erick L Y
EL
Vispé
Stéphane
S
Suzuki-Matsuda
Fumihiko
F
Uehara
Aki
A
Wada
Tadashi
T
Handa
Hiroshi
H
Satoh
Masahiko S
MS
D001667:Binding, Competitive; D002460:Cell Line; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D009687:Nuclear Proteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014779:Virus Replication; D000099253:Trans-Activation Responsive RNA-Binding Protein
D046911:Macromolecular Substances; D009687:Nuclear Proteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D042925:Positive Transcriptional Elongation Factor B; D012313:RNA; D016601:RNA-Binding Proteins; C071598:TARBP1 protein, human; D000099253:Trans-Activation Responsive RNA-Binding Protein; C499320:PARP1 protein, human