Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 20, Pages 7127-7132Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0500563102
Keywords
mitochondrial tRNA; taurine modification
Categories
Ask authors/readers for more resources
Mutations in mtDNA are responsible for a variety of mitochondrial diseases, where the mitochondrial tRNA(Leu(UUR)) gene has especially hot spots for pathogenic mutations. Clinical features often depend on the tRNA species and/or positions of the mutations; however, molecular pathogenesis elucidating the relation between the location of the mutations and their leading phenotype are not fully understood. We report here that mitochondrial tRNAS(Leu(UUR)) harboring one of five mutations found in tissues from patients with symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) (A3243G, G3244A, T3258C, T3271C, and T32911C) lacked the normal taurine-containing modification (5-taurinomethyluridine) at the anticodon wobble position. In contrast, mitochondrial tRNASLeu(UUR) with different mutations found in patients that have mitochondrial diseases but do not show the MELAS symptoms (G3242A, T3250C, C3254T, and A3280G) had the normal 5-taurinomethyluridine modifications. These observations were made by using a modified primer extension technique that can detect the modification deficiency in the extremely limited quantities of mutant tRNAs obtainable from patient tissues. These results strongly suggest deficient wobble modification could be a key molecular factor responsible for the phenotypic features of MELAS, which can explain why the different MELAS-associated mutations result in indistinguishable clinical features.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available