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

Fiche publication


Date publication

juin 2008

Auteurs

Membres identifiés du Cancéropôle Est :
Pr MELY Yves


Tous les auteurs :
Kuciak M, Gabus C, Ivanyi-Nagy R, Semrad K, Storchak R, Chaloin O, Muller S, Mely Y, Darlix JL

Résumé

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(4461) peptide identified here corresponds to the smallest known sequence with DNA/RNA chaperoning properties.

Référence

Nucleic Acids Res. 2008 Jun;36(10):3389-400