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  Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance.

Korniy, N., Goyal, A., Hoffmann, M., Samatova, E. N., Peske, F., Pöhlmann, S., et al. (2019). Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance. Nucleic Acids Research, 47(10), 5210-5222. doi:10.1093/nar/gkz202.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-6008-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-CAAD-7
Genre: Journal Article

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 Creators:
Korniy, N.1, Author              
Goyal, A.1, Author              
Hoffmann, M., Author
Samatova, E. N.1, Author              
Peske, F.1, Author              
Pöhlmann, S., Author
Rodnina, M. V.1, Author              
Affiliations:
1Department of Physical Biochemistry, MPI for Biophysical Chemistry, Max Planck Society, ou_578598              

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 Abstract: A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a -1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNALeu that reads the UUA codon at the mRNA slippery site. This tRNALeu isoacceptor is particularly rare in human cell lines derived from T-lymphocytes, the cells that are targeted by HIV-1. When UUA decoding is delayed, the frameshifting follows an alternative route, which maintains the Gag to Gag-Pol ratio constant. A second potential slippery site downstream of the first one is normally inefficient but can also support -1-frameshifting when altered by a compensatory resistance mutation in response to current antiviral drug therapy. Together these different regimes allow the virus to maintain a constant -1-frameshifting efficiency to ensure successful virus propagation.

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Language(s): eng - English
 Dates: 2019-04-102019-06-04
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1093/nar/gkz202
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Title: Nucleic Acids Research
Source Genre: Journal
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Pages: - Volume / Issue: 47 (10) Sequence Number: - Start / End Page: 5210 - 5222 Identifier: -