Initiation of HIV-1 reverse transcription and functional role of nucleocapsid-mediated tRNA/viral genome interactions.
HIV-1 reverse transcription is initiated from a tRNA(Lys)(3) molecule annealed to the viral RNA at the primer binding site (PBS). The annealing of tRNA(Lys)(3) requires the opening of its three-dimensional structure and RNA rearrangements to form an efficient initiation complex recognized by the reverse transcriptase. This annealing is mediated by the nucleocapsid protein (NC). In this paper, we first review the actual knowledge about HIV-1 viral RNA and tRNA(Lys)(3) structures. Then, we summarize the studies explaining how NC chaperones the formation of the tRNA(Lys)(3)/PBS binary complex. Additional NMR data that investigated the NC interaction with tRNA(Lys)(3) D-loop are presented. Lastly, we focused on the additional interactions occurring between tRNA(Lys)(3) and the viral RNA and showed that they are dependent on HIV-1 isolates, i.e. the sequence and the structure of the viral RNA.
Laboratoire de Cristallographie et RMN biologiques, Université Paris-Descartes, CNRS UMR 8015, 4 avenue de l'Observatoire, 75006 Paris, France.
Dona
D
Sleiman
Valérie
V
Goldschmidt
Pierre
P
Barraud
Roland
R
Marquet
Jean-Christophe
JC
Paillart
Carine
C
Tisné
D015497:HIV-1 / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D018832:Molecular Chaperones / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012357:RNA, Transfer, Lys / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D048348:Reverse Transcription; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism
D018832:Molecular Chaperones; C071884:NCP7 protein, Human immunodeficiency virus 1; D012357:RNA, Transfer, Lys; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus