title: Dealing with an Unconventional Genetic Code in  Mitochondria: The Biogenesis and Pathogenic  Defects of the 5-Formylcytosine Modification in  Mitochondrial tRNAMet.
abstract: Human mitochondria contain their own genome, which uses an unconventional genetic code. In addition to the standard AUG methionine codon, the single mitochondrial tRNA Methionine (mt-tRNAMet) also recognises AUA during translation initiation and elongation. Post-transcriptional modifications of tRNAs are important for structure, stability, correct folding and aminoacylation as well as decoding. The unique 5-formylcytosine (f5C) modification of position 34 in mt-tRNAMet has been long postulated to be crucial for decoding of unconventional methionine codons and efficient mitochondrial translation. However, the enzymes responsible for the formation of mitochondrial f5C have been identified only recently. The first step of the f5C pathway consists of methylation of cytosine by NSUN3. This is followed by further oxidation by ABH1. Here, we review the role of f5C, the latest breakthroughs in our understanding of the biogenesis of this unique mitochondrial tRNA modification and its involvement in human disease.
authors.affiliation: Mitochondrial Genetics, Medical Research Council Mitochondrial Biology Unit, University of Cambridge,  Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK. lindsey.van.haute@mrc-mbu.cam.ac.uk.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Van Haute
authors.affiliation: Mitochondrial Genetics, Medical Research Council Mitochondrial Biology Unit, University of Cambridge,  Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK. cap71@mrc-mbu.cam.ac.uk.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Powell
authors.affiliation: Mitochondrial Genetics, Medical Research Council Mitochondrial Biology Unit, University of Cambridge,  Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK. michal.minczuk@mrc-mbu.cam.ac.uk.
authors.forename: Michal
authors.initials: M
authors.lastname: Minczuk
mesh_terms: D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004194:Disease; D005815:Genetic Code; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D008954:Models, Biological; D012358:RNA, Transfer, Met / Q000378:metabolism*
chemical_list: C560973:5-formylcytosine; D012358:RNA, Transfer, Met; D003596:Cytosine
keywords: mitochondria;   translation;  5‐formylcytosine;  5‐methylcytosine;  NSUN3;  RNA modification;  tRNA