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Originally published In Press as doi:10.1074/jbc.M408435200 on October 21, 2004

J. Biol. Chem., Vol. 280, Issue 1, 448-457, January 7, 2005
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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*

Marianne Parent{ddagger}§, Tetsu M. C. Yung{ddagger}§, Ann Rancourt{ddagger}, Erick L. Y. Ho{ddagger}, Stéphane Vispé{ddagger}, Fumihiko Suzuki-Matsuda¶, Aki Uehara¶, Tadashi Wada¶, Hiroshi Handa¶, and Masahiko S. Satoh, A salary support award recipient from the Canadian Institutes of Health Research and NCIC{ddagger}||

From the {ddagger}Division of Health and Environmental Research, Laval University Medical Center (CHUL), and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, 2705 Blvd Laurier, Ste-Foy, Quebec G1V 4G2, Canada and the Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8503, Japan

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 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.


Received for publication, July 26, 2004 , and in revised form, October 13, 2004.

* This work was supported by the National Cancer Institute of Canada (NCIC) (to M. S. S.) and a grant of Research and Development Projects in Cooperation with Academic Institutions from New Energy and Industrial Technology Development Organization (NEDO) (to H. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

|| To whom correspondence should be addressed. Tel.: 418-656-4141 (ext. 47340); Fax: 418-654-2159; E-mail: Masahiko.sato{at}crchul.ulaval.ca.


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