{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:30:06Z","timestamp":1789194606206,"version":"build-2803163510"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T00:00:00Z","timestamp":1562284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00015\/4"],"award-info":[{"award-number":["MC_UU_00015\/4"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003043","name":"EMBO","doi-asserted-by":"publisher","award":["ALFT 701-2013"],"award-info":[{"award-number":["ALFT 701-2013"]}],"id":[{"id":"10.13039\/501100003043","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C3008463"],"award-info":[{"award-number":["NRF-2019R1A2C3008463"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C13474\/A18583"],"award-info":[{"award-number":["C13474\/A18583"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C6946\/A14492"],"award-info":[{"award-number":["C6946\/A14492"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104640\/Z\/14\/Z"],"award-info":[{"award-number":["104640\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092096\/Z\/10\/Z"],"award-info":[{"award-number":["092096\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs and 11 mRNAs and their post-transcriptional modification constitutes one of the key regulatory steps during mitochondrial gene expression. Cytosine-5 methylation (m5C) has been detected in mitochondrial transcriptome, however its biogenesis has not been investigated in details. Mammalian NOP2\/Sun RNA Methyltransferase Family Member 2 (NSUN2) has been characterized as an RNA methyltransferase introducing m5C in nuclear-encoded tRNAs, mRNAs and microRNAs and associated with cell proliferation and differentiation, with pathogenic variants in NSUN2 being linked to neurodevelopmental disorders. Here we employ spatially restricted proximity labelling and immunodetection to demonstrate that NSUN2 is imported into the matrix of mammalian mitochondria. Using three genetic models for NSUN2 inactivation\u2014knockout mice, patient-derived fibroblasts and CRISPR\/Cas9 knockout in human cells\u2014we show that NSUN2 is necessary for the generation of m5C at positions 48, 49 and 50 of several mammalian mitochondrial tRNAs. Finally, we show that inactivation of NSUN2 does not have a profound effect on mitochondrial tRNA stability and oxidative phosphorylation in differentiated cells. We discuss the importance of the newly discovered function of NSUN2 in the context of human disease.<\/jats:p>","DOI":"10.1093\/nar\/gkz559","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T15:15:48Z","timestamp":1562080548000},"page":"8720-8733","source":"Crossref","is-referenced-by-count":157,"title":["NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs"],"prefix":"10.1093","volume":"47","author":[{"given":"Lindsey","family":"Van\u00a0Haute","sequence":"first","affiliation":[{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Yi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Seoul National University, Gwanak-ro 1, Seoul 08826, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly J","family":"McCann","sequence":"additional","affiliation":[{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Powell","sequence":"additional","affiliation":[{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhiru","family":"Bansal","sequence":"additional","affiliation":[{"name":"Wellcome Trust\/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"},{"name":"Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Vasiliauskait\u0117","sequence":"additional","affiliation":[{"name":"STORM Therapeutics Limited, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Garone","sequence":"additional","affiliation":[{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghee","family":"Shin","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute of Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-8440","authenticated-orcid":false,"given":"Jong-Seo","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for RNA Research, Institute of Basic Science, Seoul 08826, Korea"},{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Frye","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK"},{"name":"German Cancer Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA\u00a092123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A","family":"Miska","sequence":"additional","affiliation":[{"name":"Wellcome Trust\/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK"},{"name":"Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK"},{"name":"Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Woo","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Seoul National University, Gwanak-ro 1, Seoul 08826, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Minczuk","sequence":"additional","affiliation":[{"name":"Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,5]]},"reference":[{"key":"2019103103493091100_B1","doi-asserted-by":"crossref","first-page":"D1160","DOI":"10.1093\/nar\/gkr1101","article-title":"MitoMiner: a data warehouse for mitochondrial proteomics data","volume":"40","author":"Smith","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.bbagrm.2018.11.005","article-title":"The mammalian mitochondrial epitranscriptome","volume":"1862","author":"Rebelo-Guiomar","year":"2019","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"2019103103493091100_B3","doi-asserted-by":"crossref","first-page":"e27596","DOI":"10.7554\/eLife.27596","article-title":"Maturation of selected human mitochondrial tRNAs requires deadenylation","volume":"6","author":"Pearce","year":"2017","journal-title":"Elife"},{"key":"2019103103493091100_B4","doi-asserted-by":"crossref","first-page":"7346","DOI":"10.1093\/nar\/gku390","article-title":"A complete landscape of post-transcriptional modifications in mammalian mitochondrial tRNAs","volume":"42","author":"Suzuki","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev-genet-110410-132531","article-title":"Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases","volume":"45","author":"Suzuki","year":"2011","journal-title":"Annu. Rev. Genet."},{"key":"2019103103493091100_B6","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrg2341","article-title":"DNA methylation landscapes: provocative insights from epigenomics","volume":"9","author":"Suzuki","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"2019103103493091100_B7","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1093\/nar\/gkp1117","article-title":"5-methylcytosine in RNA: detection, enzymatic formation and biological functions","volume":"38","author":"Motorin","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B8","doi-asserted-by":"crossref","first-page":"D303","DOI":"10.1093\/nar\/gkx1030","article-title":"MODOMICS: a database of RNA modification pathways. 2017 update","volume":"46","author":"Boccaletto","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1126\/science.1120976","article-title":"Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2","volume":"311","author":"Goll","year":"2006","journal-title":"Science"},{"key":"2019103103493091100_B10","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1101\/gad.586710","article-title":"RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage","volume":"24","author":"Schaefer","year":"2010","journal-title":"Genes Dev."},{"key":"2019103103493091100_B11","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.1038\/ncomms7158","article-title":"Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan","volume":"6","author":"Schosserer","year":"2015","journal-title":"Nat. Commun."},{"key":"2019103103493091100_B12","doi-asserted-by":"crossref","first-page":"e0133321","DOI":"10.1371\/journal.pone.0133321","article-title":"Eukaryotic rRNA modification by yeast 5-methylcytosine-methyltransferases and human proliferation-associated antigen p120","volume":"10","author":"Bourgeois","year":"2015","journal-title":"PLoS One"},{"key":"2019103103493091100_B13","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1261\/rna.051524.115","article-title":"NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs","volume":"21","author":"Haag","year":"2015","journal-title":"RNA"},{"key":"2019103103493091100_B14","doi-asserted-by":"crossref","first-page":"e1004110","DOI":"10.1371\/journal.pgen.1004110","article-title":"NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly","volume":"10","author":"Metodiev","year":"2014","journal-title":"PLos Genet."},{"key":"2019103103493091100_B15","doi-asserted-by":"crossref","first-page":"12039","DOI":"10.1038\/ncomms12039","article-title":"Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3","volume":"7","author":"Van\u00a0Haute","year":"2016","journal-title":"Nat. Commun."},{"key":"2019103103493091100_B16","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/nchembio.2099","article-title":"NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met)","volume":"12","author":"Nakano","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"2019103103493091100_B17","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.15252\/embj.201694885","article-title":"NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation","volume":"35","author":"Haag","year":"2016","journal-title":"EMBO J."},{"key":"2019103103493091100_B18","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.1093\/nar\/gkx354","article-title":"ALKBH1 is an RNA dioxygenase responsible for cytoplasmic and mitochondrial tRNA modifications","volume":"45","author":"Kawarada","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B19","doi-asserted-by":"crossref","first-page":"6034","DOI":"10.1093\/nar\/gkl765","article-title":"Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA)","volume":"34","author":"Brzezicha","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B20","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nsmb.2357","article-title":"RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis","volume":"19","author":"Tuorto","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2019103103493091100_B21","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/cr.2017.55","article-title":"5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader","volume":"27","author":"Yang","year":"2017","journal-title":"Cell Res."},{"key":"2019103103493091100_B22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.celrep.2013.06.029","article-title":"NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs","volume":"4","author":"Hussain","year":"2013","journal-title":"Cell Rep."},{"key":"2019103103493091100_B23","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/EBC20170103","article-title":"Mitochondrial DNA transcription and translation: clinical syndromes","volume":"62","author":"Boczonadi","year":"2018","journal-title":"Essays Biochem."},{"key":"2019103103493091100_B24","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s10545-015-9859-z","article-title":"Mitochondrial transcript maturation and its disorders","volume":"38","author":"Van\u00a0Haute","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"2019103103493091100_B25","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/s41467-018-04250-4","article-title":"CO2-sensitive tRNA modification associated with human mitochondrial disease","volume":"9","author":"Lin","year":"2018","journal-title":"Nat. Commun."},{"key":"2019103103493091100_B26","doi-asserted-by":"crossref","first-page":"e1002403","DOI":"10.1371\/journal.pgen.1002403","article-title":"The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate","volume":"7","author":"Blanco","year":"2011","journal-title":"PLos Genet."},{"key":"2019103103493091100_B27","doi-asserted-by":"crossref","first-page":"4284","DOI":"10.1093\/nar\/gkq1224","article-title":"TEFM (c17orf42) is necessary for transcription of human mtDNA","volume":"39","author":"Minczuk","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B28","doi-asserted-by":"crossref","first-page":"24356","DOI":"10.1038\/srep24356","article-title":"CRISPR-Cas9(D10A) nickase-based genotypic and phenotypic screening to enhance genome editing","volume":"6","author":"Chiang","year":"2016","journal-title":"Sci. Rep."},{"key":"2019103103493091100_B29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1042\/BJ20091714","article-title":"Novel insights into the assembly and function of human nuclear-encoded cytochrome c oxidase subunits 4, 5a, 6a, 7a and 7b","volume":"428","author":"Fornuskova","year":"2010","journal-title":"Biochem. J."},{"key":"2019103103493091100_B30","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.celrep.2016.04.064","article-title":"APEX fingerprinting reveals the subcellular localization of proteins of interest","volume":"15","author":"Lee","year":"2016","journal-title":"Cell Rep."},{"key":"2019103103493091100_B31","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1021\/jacs.6b10418","article-title":"Architecture mapping of the inner mitochondrial membrane proteome by chemical tools in live cells","volume":"139","author":"Lee","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"2019103103493091100_B32","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nprot.2009.245","article-title":"Construction and testing of engineered zinc-finger proteins for sequence-specific modification of mtDNA","volume":"5","author":"Minczuk","year":"2010","journal-title":"Nat. Protoc."},{"key":"2019103103493091100_B33","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"2019103103493091100_B34","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1126\/science.1230593","article-title":"Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging","volume":"339","author":"Rhee","year":"2013","journal-title":"Science"},{"key":"2019103103493091100_B35","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nprot.2016.018","article-title":"Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2","volume":"11","author":"Hung","year":"2016","journal-title":"Nat. Protoc."},{"key":"2019103103493091100_B36","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.cub.2006.04.027","article-title":"The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors","volume":"16","author":"Frye","year":"2006","journal-title":"Curr. Biol."},{"key":"2019103103493091100_B37","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41594-019-0218-x","article-title":"Genome-wide identification of mRNA 5-methylcytosine in mammals","volume":"26","author":"Huang","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2019103103493091100_B38","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1136\/jmedgenet-2011-100686","article-title":"Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome","volume":"49","author":"Martinez","year":"2012","journal-title":"J. Med. Genet."},{"key":"2019103103493091100_B39","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.15252\/embj.201489282","article-title":"Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders","volume":"33","author":"Blanco","year":"2014","journal-title":"EMBO J."},{"key":"2019103103493091100_B40","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1086\/421530","article-title":"Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA)","volume":"74","author":"Bykhovskaya","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B41","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1093\/hmg\/ddx314","article-title":"Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome","volume":"26","author":"Garone","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2019103103493091100_B42","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.ajhg.2012.04.011","article-title":"Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis","volume":"90","author":"Ghezzi","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B43","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.ajhg.2014.10.017","article-title":"Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy","volume":"95","author":"Kopajtich","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B44","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.biocel.2013.01.005","article-title":"Mitochondria: mitochondrial RNA metabolism and human disease","volume":"45","author":"Nicholls","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2019103103493091100_B45","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ajhg.2015.06.011","article-title":"TRMT5 mutations cause a defect in Post-transcriptional modification of mitochondrial tRNA associated with multiple Respiratory-Chain deficiencies","volume":"97","author":"Powell","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B46","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13023-016-0477-0","article-title":"TRNT1 deficiency: clinical, biochemical and molecular genetic features","volume":"11","author":"Wedatilake","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"2019103103493091100_B47","doi-asserted-by":"crossref","first-page":"e1004424","DOI":"10.1371\/journal.pgen.1004424","article-title":"Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA","volume":"10","author":"Yarham","year":"2014","journal-title":"PLos Genet."},{"key":"2019103103493091100_B48","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ajhg.2009.08.004","article-title":"Acute infantile liver failure due to mutations in the TRMU gene","volume":"85","author":"Zeharia","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B49","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1182\/blood-2014-08-591370","article-title":"Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD)","volume":"124","author":"Chakraborty","year":"2014","journal-title":"Blood"},{"key":"2019103103493091100_B50","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1038\/s41467-018-06471-z","article-title":"RNA modification landscape of the human mitochondrial tRNA(Lys) regulates protein synthesis","volume":"9","author":"Richter","year":"2018","journal-title":"Nat. Commun."},{"key":"2019103103493091100_B51","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0014-5793(00)01145-5","article-title":"Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNA(Lys) with the MERRF encephalomyopathy pathogenic mutation","volume":"467","author":"Yasukawa","year":"2000","journal-title":"FEBS Lett."},{"key":"2019103103493091100_B52","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1074\/jbc.M116.771105","article-title":"The pseudouridine synthase RPUSD4 is an essential component of mitochondrial RNA granules","volume":"292","author":"Zaganelli","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2019103103493091100_B53","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1091\/mbc.e14-01-0014","article-title":"MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome","volume":"25","author":"Rorbach","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"2019103103493091100_B54","doi-asserted-by":"crossref","first-page":"24936","DOI":"10.1074\/jbc.C114.581868","article-title":"Assignment of 2\u2032-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16 S ribosomal RNA (rRNA)","volume":"289","author":"Lee","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2019103103493091100_B55","doi-asserted-by":"crossref","first-page":"e1002557","DOI":"10.1371\/journal.pbio.1002557","article-title":"Mitochondrial 16S rRNA is methylated by tRNA methyltransferase TRMT61B in all vertebrates","volume":"14","author":"Bar-Yaacov","year":"2016","journal-title":"PLoS Biol."},{"key":"2019103103493091100_B56","doi-asserted-by":"crossref","first-page":"e00214-17","DOI":"10.1128\/MCB.00214-17","article-title":"TRMT1-catalyzed tRNA modifications are required for redox homeostasis to ensure proper cellular proliferation and oxidative stress survival","volume":"37","author":"Dewe","year":"2017","journal-title":"Mol. Cell Biol."},{"key":"2019103103493091100_B57","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1261\/rna.574407","article-title":"Mg2+ binding and archaeosine modification stabilize the G15 C48 Levitt base pair in tRNAs","volume":"13","author":"Oliva","year":"2007","journal-title":"RNA"},{"key":"2019103103493091100_B58","doi-asserted-by":"crossref","first-page":"11012","DOI":"10.1021\/bi00160a010","article-title":"The role of 5-methylcytidine in the anticodon arm of yeast tRNA(Phe): site-specific Mg2+ binding and coupled conformational transition in DNA analogs","volume":"31","author":"Dao","year":"1992","journal-title":"Biochemistry"},{"key":"2019103103493091100_B59","doi-asserted-by":"crossref","first-page":"e1004639","DOI":"10.1371\/journal.pgen.1004639","article-title":"tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells","volume":"10","author":"Okamoto","year":"2014","journal-title":"PLos Genet."},{"key":"2019103103493091100_B60","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/nar\/22.3.347","article-title":"Higher-order structure of bovine mitochondrial tRNA(Phe) lacking the \u2018conserved\u2019 GG and T psi CG sequences as inferred by enzymatic and chemical probing","volume":"22","author":"Wakita","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"2019103103493091100_B61","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.ajhg.2012.03.021","article-title":"Mutations in NSUN2 cause autosomal-recessive intellectual disability","volume":"90","author":"Abbasi-Moheb","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B62","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.ajhg.2012.03.023","article-title":"Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability","volume":"90","author":"Khan","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"2019103103493091100_B63","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10545-012-9487-9","article-title":"Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients","volume":"36","author":"Cassandrini","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"2019103103493091100_B64","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s10545-011-9413-6","article-title":"Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2","volume":"35","author":"Glamuzina","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"2019103103493091100_B65","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/humu.22590","article-title":"VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies","volume":"35","author":"Diodato","year":"2014","journal-title":"Hum. Mutat."},{"key":"2019103103493091100_B66","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1136\/archdischild-2016-311370","article-title":"Recognition, investigation and management of mitochondrial disease","volume":"102","author":"Davison","year":"2017","journal-title":"Arch. Dis. Child."},{"key":"2019103103493091100_B67","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1128\/MCB.01523-12","article-title":"The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation","volume":"33","author":"Hussain","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"2019103103493091100_B68","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.stemcr.2016.11.014","article-title":"Cytosine-5 RNA Methylation Regulates Neural Stem Cell Differentiation and Motility","volume":"8","author":"Flores","year":"2017","journal-title":"Stem Cell Reports"},{"key":"2019103103493091100_B69","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1387\/ijdb.103198ap","article-title":"Modulation of mitochondrial biogenesis and bioenergetic metabolism upon in vitro and in vivo differentiation of human ES and iPS cells","volume":"54","author":"Prigione","year":"2010","journal-title":"Int. J. Dev. Biol."},{"key":"2019103103493091100_B70","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1242\/dev.091777","article-title":"Stem cell metabolism in tissue development and aging","volume":"140","author":"Shyh-Chang","year":"2013","journal-title":"Development"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/47\/16\/8720\/30335505\/gkz559.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/47\/16\/8720\/30335505\/gkz559.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T03:50:02Z","timestamp":1572493802000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/47\/16\/8720\/5528740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,5]]},"references-count":70,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,7,5]]},"published-print":{"date-parts":[[2019,9,19]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkz559","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/626960","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9,19]]},"published":{"date-parts":[[2019,7,5]]}}}