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The resistance is due to the ability of these bacteria to block antibiotics from permeating into and accumulating inside the cell, while the persistence is due to the ability of these bacteria to enter into a nonreplicating state that shuts down major metabolic pathways but remains active in drug efflux. Resistance and persistence are permitted by the unique cell envelope structure of Gram\u2010negative bacteria, which consists of both an outer and an inner membrane (OM and IM, respectively) that lay above and below the cell wall. Unexpectedly, recent work reveals that m<jats:sup>1<\/jats:sup>G37 methylation of tRNA, at the <jats:italic>N<\/jats:italic><jats:sup>1<\/jats:sup> of guanosine at position 37 on the 3\u2032\u2010side of the tRNA anticodon, controls biosynthesis of both membranes and determines the integrity of cell envelope structure, thus providing a novel link to the development of bacterial resistance and persistence to antibiotics. The impact of m<jats:sup>1<\/jats:sup>G37\u2010tRNA methylation on Gram\u2010negative bacteria can reach further, by determining the ability of these bacteria to exit from the persistence state when the antibiotic treatment is removed. These conceptual advances raise the possibility that successful targeting of m<jats:sup>1<\/jats:sup>G37\u2010tRNA methylation can provide new approaches for treating acute and chronic infections caused by Gram\u2010negative bacteria.<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>Translation &gt; Translation Regulation<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA Processing &gt; RNA Editing and Modification<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA Structure and Dynamics &gt; Influence of RNA Structure in Biological Systems<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.1609","type":"journal-article","created":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T13:45:28Z","timestamp":1592055928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<scp>tRNA<\/scp> methylation: An unexpected link to bacterial resistance and persistence to antibiotics and beyond"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6546-2597","authenticated-orcid":false,"given":"Ya\u2010Ming","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9385-4424","authenticated-orcid":false,"given":"Isao","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-4817","authenticated-orcid":false,"given":"Leonard J.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, and Michael Smith 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