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van Haute, L.* ; Dietmann, S.* ; Kremer, L.S. ; Hussain, S.* ; Pearce, S.F.* ; Powell, C.A.* ; Rorbach, J.* ; Lantaff, R.* ; Blanco, S.* ; Sauer, S.* ; Kotzaeridou, U.* ; Hoffmann, G.F.* ; Memari, Y.* ; Kolb-Kokocinski, A.* ; Durbin, R.* ; Mayr, J.A.* ; Frye, M.* ; Prokisch, H. ; Minczuk, M.*

Deficient methylation and formylation of mt-tRNAMet wobble cytosine in a patient carrying mutations in NSUN3.

Nat. Commun. 7:12039 (2016)
Publ. Version/Full Text Research data DOI PMC
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Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m(5)C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNA(Met)). Further, we demonstrate that m(5)C deficiency in mt-tRNA(Met) results in the lack of 5-formylcytosine (f(5)C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f(5)C in human mitochondrial RNA is generated by oxidative processing of m(5)C.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Methyltransferase Misu Nsun2; Mitochondrial Transfer-rnas; Hypertrophic Cardiomyopathy; Noncoding Rna; Bovine Liver; Dna; 5-methylcytosine; 5-formylcytosine; Anticodon; Genome
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 12039 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
PubMed ID 27356879
DOI 10.1038/ncomms12039
WOS ID WOS:000379110800001
Scopus ID 84977138242
Erfassungsdatum 2016-07-09
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