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Nucleic Acids Research Advance Access published online on April 28, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn177
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro

Monika Kuciak1, Caroline Gabus1, Roland Ivanyi-Nagy1, Katharina Semrad2, Roman Storchak3, Olivier Chaloin4, Sylviane Muller4, Yves Mély3 and Jean-Luc Darlix1,*

1LaboRetro INSERM #758, Ecole Normale Supérieure de Lyon, IFR 128 Biosciences Lyon-Gerland, 69364 Lyon Cedex 07, France, 2Max F. Perutz Laboratories, University of Vienna, Austria, 3Département de Pharmacologie et Physico-chimie, UMR 7175 CNRS, Institut Gilbert Laustriat, Université Louis Pasteur, 74 route du Rhin, 67401 Illkirch and 4CNRS, Immunologie et Chimie Therapeutiques, UPR 9021, Institut de Biologie Moleculaire et Cellulaire (IBMC) 15 rue René Descartes, 67000 Strasbourg, France

*To whom correspondence should be addressed. Tel: +33 4 72 72 81 69; Fax: +33 4 72 72 81 37; Email: jldarlix{at}ens-lyon.fr

Received January 10, 2008. Revised March 27, 2008. Accepted March 27, 2008.

The human immunodeficiency virus type 1 (HIV-1) is a primate lentivirus that causes the acquired immunodeficiency syndrome (AIDS). In addition to the virion structural proteins and enzyme precursors, that are Gag, Env and Pol, HIV-1 encodes several regulatory proteins, notably a small nuclear transcriptional activator named Tat. The Tat protein is absolutely required for virus replication since it controls proviral DNA transcription to generate the full-length viral mRNA. Tat can also regulate mRNA capping and splicing and was recently found to interfere with the cellular mi- and siRNA machinery. Because of its extensive interplay with nucleic acids, and its basic and disordered nature we speculated that Tat had nucleic acid-chaperoning properties. This prompted us to examine in vitro the nucleic acid-chaperoning activities of Tat and Tat peptides made by chemical synthesis. Here we report that Tat has potent nucleic acid-chaperoning activities according to the standard DNA annealing, DNA and RNA strand exchange, RNA ribozyme cleavage and trans-splicing assays. The active Tat(44–61) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties.


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