title: Cross-Talk between Dnmt2-Dependent tRNA Methylation and Queuosine Modification.
abstract: Enzymes of the Dnmt2 family of methyltransferases have yielded a number of unexpected discoveries. The first surprise came more than ten years ago when it was realized that, rather than being DNA methyltransferases, Dnmt2 enzymes actually are transfer RNA (tRNA) methyltransferases for cytosine-5 methylation, foremost C38 (m5C38) of tRNAAsp. The second unanticipated finding was our recent discovery of a nutritional regulation of Dnmt2 in the fission yeast Schizosaccharomyces pombe. Significantly, the presence of the nucleotide queuosine in tRNAAsp strongly stimulates Dnmt2 activity both in vivo and in vitro in S. pombe. Queuine, the respective base, is a hypermodified guanine analog that is synthesized from guanosine-5'-triphosphate (GTP) by bacteria. Interestingly, most eukaryotes have queuosine in their tRNA. However, they cannot synthesize it themselves, but rather salvage it from food or from gut microbes. The queuine obtained from these sources comes from the breakdown of tRNAs, where the queuine ultimately was synthesized by bacteria. Queuine thus has been termed a micronutrient. This review summarizes the current knowledge of Dnmt2 methylation and queuosine modification with respect to translation as well as the organismal consequences of the absence of these modifications. Models for the functional cooperation between these modifications and its wider implications are discussed.
authors.affiliation: Institut für Biologie, Humboldt-Universität zu Berlin, 10099 Berlin, Germany. ann.ehrenhofer-murray@hu-berlin.de.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Ehrenhofer-Murray
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008745:Methylation; D009704:Nucleoside Q / Q000737:chemistry* / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism
chemical_list: D009704:Nucleoside Q; D012343:RNA, Transfer; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: Dnmt2; Pmt1; anticodon modification; epitranscriptomics; queuine; queuosine; tRNA cleavage; translation