Mitochondrial tRNA super(Leu) isoforms in lung carcinoma cybrid cells containing the np 3243 mtDNA mutation

We have investigated the representation of structural isoforms of the two mitochondrial leucyl tRNAs in lung carcinoma cybrid cell lines containing the np 3243 (MELAS) mtDNA mutation, alone or in combination with the np 12300 suppressor mutation. The mutant tRNA super(Leu)(UUR) is aminoacylated very...

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Bibliographic Details
Published in:Human molecular genetics 1998-12, Vol.7 (13), p.2141-2147
Main Authors: El Meziane, A, Lehtinen, S K, Holt, I J, Jacobs, H T
Format: Article
Language:English
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Summary:We have investigated the representation of structural isoforms of the two mitochondrial leucyl tRNAs in lung carcinoma cybrid cell lines containing the np 3243 (MELAS) mtDNA mutation, alone or in combination with the np 12300 suppressor mutation. The mutant tRNA super(Leu)(UUR) is aminoacylated very poorly or not at all, whereas the suppressor tRNA super(Leu)(CUN) is efficiently aminoacylated. Deacylated mitochondrial tRNA super(Leu)(CUN) is present, in all human cells tested, in two structural isoforms that are separable on denaturing gels, indicating a difference in primary structure. The ratio of the two isoforms differs between cell types and is strongly biased towards one isoform in lung carcinoma cybrids containing high levels of the np 3243 mutation, compared with control cybrids. We propose that structural modification of tRNA super(Leu)(CUN) could be a natural suppression mechanism for the np 3243 and other mitochondrial tRNA super(Leu)(UUR) mutations and could underlie some of the phenotypic variability of np 3243 disease.
ISSN:0964-6906