Biochemistry Seminar

Dr. Lawrence Kleiman
Professor
Departments of Medicine & Microbiology and Immunology - McGill
Lady Davis Institute for Medical Research
Jewish General Hospital

"The Regulation of tRNALys3 annealing to HIV-1 genomic RNA"

During HIV-1 assembly, tRNALys3 anneals to viral RNA, and upon new viral infection, serves as the primer for the initiation of reverse transcription of viral RNA into proviral DNA. Regulation of tRNALys3 annealing during viral assembly involves several factors: 1) A selective concentration of tRNALys3 at the cellular site of viral assembly, promoted by a specific interaction between viral Gag and lysyl-tRNA synthetase. 2) A configura-tion of viral Gag and GagPol that promotes the transfer of tRNALys3 from lysyl tRNA synthetase to reverse transcriptase to viral RNA. 3) Viral and host cell factors that facilitate RNA annealing, such as viral nucleocapsid sequences and RNA helicase A. tRNALys3 annealing appears to be a multi-step process, where the initial stage is carried out by viral Gag before viral budding and viral protein processing, and a final stage consisting of the re-annealing of Gag-annealed tRNALys3 by mature nucleocapsid, NCp7.

References:

Kleiman,L. Jones, C., and Musier-Forsyth, K. Formation of the tRNALys Packaging Complex in HIV-1 (2009) FEBS Lett. 584: 359-365

Guo, F., Saadatmand, J., Niu, M., and Kleiman, L. Roles of Gag and NCp7 in facilitating tRNALys3 annealing to viral RNA in HIV-1. (2009) J. Virol. 83: 8099-8107

Halwani,  R., Cen, S.,  Javanbakht,  H., Saadatmand,  J., Kim, S., Shiba, K., and Kleiman,L. Cellular distribution of lysyl-tRNA synthetase and its interaction with Gag during HIV-1 assembly. (2004) J. Virol. 78: 7553-7564

Javanbakht, H., Halwani, R., Cen, S., Sadaatmand, J., Musier-Forsyth, K., Gottlinger, H., and Kleiman, L. The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly. (2003) J. Biol. Chem. 278: 27644-27651