title: The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro.
abstract: 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.
authors.affiliation: LaboRetro INSERM #758, Ecole Normale Supérieure de Lyon, IFR 128 Biosciences Lyon-Gerland, 69364 Lyon Cedex 07, France.
authors.forename: Monika
authors.initials: M
authors.lastname: Kuciak
authors.forename: Caroline
authors.initials: C
authors.lastname: Gabus
authors.forename: Roland
authors.initials: R
authors.lastname: Ivanyi-Nagy
authors.forename: Katharina
authors.initials: K
authors.lastname: Semrad
authors.forename: Roman
authors.initials: R
authors.lastname: Storchak
authors.forename: Olivier
authors.initials: O
authors.lastname: Chaloin
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Yves
authors.initials: Y
authors.lastname: Mély
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Darlix
mesh_terms: D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D016337:RNA, Catalytic; D020040:Trans-Splicing; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D018832:Molecular Chaperones; D010455:Peptides; D016337:RNA, Catalytic; C427204:hammerhead ribozyme; D054322:tat Gene Products, Human Immunodeficiency Virus; D012313:RNA