Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients

G. Valentin Börner, Massimo Zeviani, Valeria Tiranti, Franco Carrara, Sabine Hoffmann, Klaus Dieter Gerbitz, Hanns Lochmüller, Dieter Pongratz, Thomas Klopstock, Atle Melberg, Elisabeth Holme, Svante Pääbo

Research output: Contribution to journalArticlepeer-review


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 (mitochondrial 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.

Original languageEnglish
Pages (from-to)467-475
Number of pages9
JournalHuman Molecular Genetics
Issue number4
Publication statusPublished - Mar 1 2000

ASJC Scopus subject areas

  • Genetics


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