title: Pathology-related mutation A7526G (A9G) helps in the understanding of the 3D structural core of human mitochondrial tRNA(Asp).
abstract: More than 130 mutations in human mitochondrial tRNA (mt-tRNA) genes have been correlated with a variety of neurodegenerative and neuromuscular disorders. Their molecular impacts are of mosaic type, affecting various stages of tRNA biogenesis, structure, and/or functions in mt-translation. Knowledge of mammalian mt-tRNA structures per se remains scarce however. Primary and secondary structures deviate from classical tRNAs, while rules for three-dimensional (3D) folding are almost unknown. Here, we take advantage of a myopathy-related mutation A7526G (A9G) in mt-tRNA(Asp) to investigate both the primary molecular impact underlying the pathology and the role of nucleotide 9 in the network of 3D tertiary interactions. Experimental evidence is presented for existence of a 9-12-23 triple in human mt-tRNA(Asp) with a strongly conserved interaction scheme in mammalian mt-tRNAs. Mutation A7526G disrupts the triple interaction and in turn reduces aspartylation efficiency.
authors.forename: Marie
authors.initials: M
authors.lastname: Messmer
authors.forename: Agnès
authors.initials: A
authors.lastname: Gaudry
authors.forename: Marie
authors.initials: M
authors.lastname: Sissler
authors.forename: Catherine
authors.initials: C
authors.lastname: Florentz
mesh_terms: D001665:Binding Sites / Q000235:genetics; D006801:Humans; D007700:Kinetics; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008958:Models, Molecular; D020125:Mutation, Missense; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000077278:RNA, Mitochondrial; D012349:RNA, Transfer, Asp / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D046249:Transfer RNA Aminoacylation / Q000235:genetics
chemical_list: D000077278:RNA, Mitochondrial; D012349:RNA, Transfer, Asp; D012313:RNA