title: Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients.
abstract: Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mito- chondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and MERRF syndrome (myoclonus epilepsy with ragged red fibers), respectively. In most, but not all, biopsies from MELAS patients carrying the A3243G substitution in the mitochondrial tRNA(Leu(UUR))gene, the mutant tRNA is under-represented among processed and/or aminoacylated tRNAs. In contrast, in biopsies from MERRF patients harboring the A8344G substitution in the tRNA(Lys)gene neither the relative abundance nor the aminoacylation of the mutated tRNA is affected. Thus, whereas the A3243G mutation may contribute to the pathogenesis of MELAS by reducing the amount of aminoacylated tRNA(Leu), the A8344G mutation does not affect tRNA(Lys)function in the same way.
authors.affiliation: Max-Planck-Institute for Evolutionary Anthropology, Inselstrasse 22, D-04103 Leipzig, Germany. boerner@fas.harvard.edu
authors.forename: G V
authors.initials: GV
authors.lastname: Börner
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
authors.forename: V
authors.initials: V
authors.lastname: Tiranti
authors.forename: F
authors.initials: F
authors.lastname: Carrara
authors.forename: S
authors.initials: S
authors.lastname: Hoffmann
authors.forename: K D
authors.initials: KD
authors.lastname: Gerbitz
authors.forename: H
authors.initials: H
authors.lastname: Lochmüller
authors.forename: D
authors.initials: D
authors.lastname: Pongratz
authors.forename: T
authors.initials: T
authors.lastname: Klopstock
authors.forename: A
authors.initials: A
authors.lastname: Melberg
authors.forename: E
authors.initials: E
authors.lastname: Holme
authors.forename: S
authors.initials: S
authors.lastname: Pääbo
mesh_terms: D000215:Acylation; D000328:Adult; D002460:Cell Line; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006822:Hybrid Cells; D017241:MELAS Syndrome / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D017354:Point Mutation; D012313:RNA / Q000378:metabolism; D000079962:RNA, Circular; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012349:RNA, Transfer, Asp / Q000378:metabolism; D012356:RNA, Transfer, Leu / Q000235:genetics* / Q000378:metabolism
chemical_list: D000079962:RNA, Circular; D012346:RNA, Transfer, Amino Acyl; D012349:RNA, Transfer, Asp; D012356:RNA, Transfer, Leu; D012313:RNA