TY  - JOUR
A1  - Van Haute, Lindsey
A1  - Dietmann, Sabine
A1  - Kremer, Laura
A1  - Hussain, Shobbir
A1  - Pearce, Sarah F.
A1  - Powell, Christopher A.
A1  - Rorbach, Joanna
A1  - Lantaff, Rebecca
A1  - Blanco, Sandra
A1  - Sauer, Sascha
A1  - Kotzaeridou, Urania
A1  - Hoffmann, Georg F.
A1  - Memari, Yasin
A1  - Kolb-Kokocinski, Anja
A1  - Durbin, Richard
A1  - Mayr, Johannes A.
A1  - Frye, Michaela
A1  - Prokisch, Holger
A1  - Minczuk, Michal
T1  - Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3
JF  - Nature Communications
N2  - 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 (m5C) methyltransferase NSun3 and link m5C 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 m5C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNAMet). Further, we demonstrate that m5C deficiency in mt-tRNAMet results in the lack of 5-formylcytosine (f5C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f5C in human mitochondrial RNA is generated by oxidative processing of m5C.
KW  - Methylation
KW  - RNA
KW  - Transferases
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165998
VL  - 7
ER  -