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

• DOI: 10.1038/ncomms12039
• Publication Date: 2016-06-30T09:12:09Z
• Authors: Lindsey Van Haute; Sabine Dietmann; Laura Kremer; Shobbir Hussain; Sarah F. Pearce; Christopher A. Po...; Joanna Rorbach; Rebecca Lantaff; Sandra Blanco; Sascha Sauer; Urania Kotzaeridou; Georg F. Hoffmann; Yasin Memari; Anja Kolb-Kokocinski; Richard Durbin; Johannes A. Mayr; Michaela Frye; Holger Prokisch; Michal Minczuk
• Keywords: 5-Methylcytosine; Wobble base pair; Cytosine

Abstract Epitranscriptome modifications are required for structure and function of RNA defects in these pathways have been associated with human disease. Here we identify the target previously uncharacterized 5-methylcytosine (m 5 C) methyltransferase NSun3 link m C energy metabolism. Using whole-exome sequencing, identified loss-of-function mutations NSUN3 a patient presenting combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe translation that can be rescued by exogenous expression NSun3. We show is deposition at anticodon loop mitochondrially encoded transfer methionine (mt-tRNA Met ). Further, demonstrate deficiency mt-tRNA results lack 5-formylcytosine (f same tRNA position. Our findings necessary efficient reveal f generated oxidative processing C.