{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:34:47Z","timestamp":1790483687561,"version":"4.1.0"},"reference-count":68,"publisher":"Cold Spring Harbor Laboratory","issue":"3","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM052347"],"award-info":[{"award-number":["GM052347"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["RNA"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>The 3-methylcytidine (m<jats:sup>3<\/jats:sup>C) modification is ubiquitous in eukaryotic tRNA, widely found at C<jats:sub>32<\/jats:sub> in the anticodon loop of tRNA<jats:sup>Thr<\/jats:sup>, tRNA<jats:sup>Ser<\/jats:sup>, and some tRNA<jats:sup>Arg<\/jats:sup> species, as well as in the variable loop (V-loop) of certain tRNA<jats:sup>Ser<\/jats:sup> species. In the yeast <jats:italic>Saccharomyces cerevisiae<\/jats:italic>, formation of m<jats:sup>3<\/jats:sup>C<jats:sub>32<\/jats:sub> requires Trm140 for six tRNA substrates, including three tRNA<jats:sup>Thr<\/jats:sup> species and three tRNA<jats:sup>Ser<\/jats:sup> species, whereas in <jats:italic>Schizosaccharomyces pombe<\/jats:italic>, two Trm140 homologs are used, one for tRNA<jats:sup>Thr<\/jats:sup> and one for tRNA<jats:sup>Ser<\/jats:sup>. The occurrence of a single Trm140 homolog is conserved broadly among Ascomycota, whereas multiple Trm140-related homologs are found in metazoans and other fungi. We investigate here how <jats:italic>S. cerevisiae<\/jats:italic> Trm140 protein recognizes its six tRNA substrates. We show that Trm140 has two modes of tRNA substrate recognition. Trm140 recognizes G<jats:sub>35<\/jats:sub>-U<jats:sub>36<\/jats:sub>-t<jats:sup>6<\/jats:sup>A<jats:sub>37<\/jats:sub> of the anticodon loop of tRNA<jats:sup>Thr<\/jats:sup> substrates, and this sequence is an identity element because it can be used to direct m<jats:sup>3<\/jats:sup>C modification of tRNA<jats:sup>Phe<\/jats:sup>. However, Trm140 recognition of tRNA<jats:sup>Ser<\/jats:sup> substrates is different, since their anticodons do not share G<jats:sub>35<\/jats:sub>\u2013U<jats:sub>36<\/jats:sub> and do not have any nucleotides in common. Rather, specificity of Trm140 for tRNA<jats:sup>Ser<\/jats:sup> is achieved by seryl-tRNA synthetase and the distinctive tRNA<jats:sup>Ser<\/jats:sup> V-loop, as well as by t<jats:sup>6<\/jats:sup>A<jats:sub>37<\/jats:sub> and i<jats:sup>6<\/jats:sup>A<jats:sub>37<\/jats:sub>. We provide evidence that all of these components are important in vivo and that seryl-tRNA synthetase greatly stimulates m<jats:sup>3<\/jats:sup>C modification of tRNA<jats:sup>Ser(CGA)<\/jats:sup> and tRNA<jats:sup>Ser(UGA)<\/jats:sup> in vitro. In addition, our results show that Trm140 binding is a significant driving force for tRNA modification and suggest separate contributions from each recognition element for the modification.<\/jats:p>","DOI":"10.1261\/rna.059667.116","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T02:11:25Z","timestamp":1482372685000},"page":"406-419","source":"Crossref","is-referenced-by-count":70,"title":["<i>S. cerevisiae<\/i> Trm140 has two recognition modes for 3-methylcytidine modification of the anticodon loop of tRNA substrates"],"prefix":"10.1261","volume":"23","author":[{"given":"Lu","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"D'Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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