Cooperative methylation of human tRNA3Lys at positions A58 and U54 drives the early and late steps of HIV-1 replication.

Nucleic Acids Research
Hiroyuki FukudaKazuhito Tomizawa

Abstract

Retroviral infection requires reverse transcription, and the reverse transcriptase (RT) uses cellular tRNA as its primer. In humans, the TRMT6-TRMT61A methyltransferase complex incorporates N1-methyladenosine modification at tRNA position 58 (m1A58); however, the role of m1A58 as an RT-stop site during retroviral infection has remained questionable. Here, we constructed TRMT6 mutant cells to determine the roles of m1A in HIV-1 infection. We confirmed that tRNA3Lys m1A58 was required for in vitro plus-strand strong-stop by RT. Accordingly, infectivity of VSV-G pseudotyped HIV-1 decreased when the virus contained m1A58-deficient tRNA3Lys instead of m1A58-modified tRNA3Lys. In TRMT6 mutant cells, the global protein synthesis rate was equivalent to that of wild-type cells. However, unexpectedly, plasmid-derived HIV-1 expression showed that TRMT6 mutant cells decreased accumulation of HIV-1 capsid, integrase, Tat, Gag, and GagPol proteins without reduction of HIV-1 RNAs in cells, and fewer viruses were produced. Moreover, the importance of 5,2'-O-dimethyluridine at U54 of tRNA3Lys as a second RT-stop site was supported by conservation of retroviral genome-tRNALys sequence-complementarity, and TRMT6 was required for efficient 5-methy...Continue Reading

References

Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·B P Burnett, C S McHenry
Jan 1, 1974·Nucleic Acids Research·H J GrossU L Raj Bhandary
May 11, 2002·RNA·Marcus J O Johansson, Anders S Byström
Jul 11, 2003·Nucleic Acids Research·Ekaterina I ZagryadskayaSergey V Steinberg
May 18, 2004·Genes & Development·Sujatha KadabaJames Anderson
Dec 1, 2005·The Journal of Biological Chemistry·Naoki ShigiKimitsuna Watanabe
Nov 4, 2008·Cell Host & Microbe·Honglin ZhouAmy S Espeseth
Jan 11, 2011·Molecular Biology and Evolution·Anna van WeringhXuhua Xia
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
May 4, 2016·Nature Reviews. Genetics·Michaela FryeTsutomu Suzuki
May 31, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Ryota YamagamiHiroyuki Hori
Oct 11, 2016·Scientific Reports·Ann BaeyensBruno Verhasselt
Nov 7, 2017·Nucleic Acids Research·Pietro BoccalettoJanusz M Bujnicki
Apr 12, 2018·Cell Reports·Chien-Wen Chen, Motomasa Tanaka
Sep 12, 2018·Nature Cell Biology·Yilei ZhangBoyi Gan
Jan 31, 2019·Nucleic Acids Research·Valérie de Crécy-LagardJanusz M Bujnicki
Feb 1, 2019·The Journal of Biological Chemistry·Danni Jin, Karin Musier-Forsyth
Jun 20, 2019·Scientific Reports·Anna ŠimonováHana Cahová
Jul 31, 2019·Nucleic Acids Research·Jean-Michel CarterShobbir Hussain
Apr 9, 2020·Cell Reports·Mayumi HirayamaKazuhito Tomizawa
May 12, 2020·Nucleic Acids Research·Elisa VilardoWalter Rossmanith

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