title: Dynamic modulation of Dnmt2-dependent tRNA methylation by the micronutrient queuine.
abstract: Dnmt2 enzymes are cytosine-5 methyltransferases that methylate C38 of several tRNAs. We report here that the activities of two Dnmt2 homologs, Pmt1 from Schizosaccharomyces pombe and DnmA from Dictyostelium discoideum, are strongly stimulated by prior queuosine (Q) modification of the substrate tRNA. In vivo tRNA methylation levels were stimulated by growth of cells in queuine-containing medium; in vitro Pmt1 activity was enhanced on Q-containing RNA; and queuine-stimulated in vivo methylation was abrogated by the absence of the enzyme that inserts queuine into tRNA, eukaryotic tRNA-guanine transglycosylase. Global analysis of tRNA methylation in S. pombe showed a striking selectivity of Pmt1 for tRNA(Asp) methylation, which distinguishes Pmt1 from other Dnmt2 homologs. The present analysis also revealed a novel Pmt1- and Q-independent tRNA methylation site in S. pombe, C34 of tRNA(Pro). Notably, queuine is a micronutrient that is scavenged by higher eukaryotes from the diet and gut microflora. This work therefore reveals an unanticipated route by which the environment can modulate tRNA modification in an organism.
authors.affiliation: Institut für Biologie, Humboldt-Universität zu Berlin, 10115 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Hartmann
authors.affiliation: Abteilung für Genetik, Universität Kassel, 34132 Kassel, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schuster
authors.affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bender
authors.affiliation: Institut für Pharmakologie und Biochemie, Johannes Gutenberg-Universität Mainz, 55099 Mainz, Germany.
authors.forename: Kathrin L
authors.initials: KL
authors.lastname: Thüring
authors.affiliation: Institut für Pharmakologie und Biochemie, Johannes Gutenberg-Universität Mainz, 55099 Mainz, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Helm
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Katze
authors.affiliation: Abteilung für Genetik, Universität Kassel, 34132 Kassel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nellen
authors.affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lyko
authors.affiliation: Institut für Biologie, Humboldt-Universität zu Berlin, 10115 Berlin, Germany ann.ehrenhofer-murray@hu-berlin.de.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Ehrenhofer-Murray
mesh_terms: D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D004023:Dictyostelium / Q000201:enzymology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008745:Methylation; D018977:Micronutrients / Q000378:metabolism*; D010430:Pentosyltransferases / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism*; D012349:RNA, Transfer, Asp / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
chemical_list: D018977:Micronutrients; D012349:RNA, Transfer, Asp; D029702:Schizosaccharomyces pombe Proteins; D006147:Guanine; C019549:queuine; D012343:RNA, Transfer; D004248:DNA (Cytosine-5-)-Methyltransferases; C578376:Pmt1 protein, S pombe; D010430:Pentosyltransferases; C020837:queuine tRNA-ribosyltransferase