A. El Meziane et al., Mitochondrial tRNA(Leu) isoforms in lung carcinoma cybrid cells containingthe np 3243 mtDNA mutation, HUM MOL GEN, 7(13), 1998, pp. 2141-2147
We have investigated the representation of structural isoforms of the two m
itochondrial leucyl tRNAs in lung carcinoma cybrid cell lines containing th
e np 3243 (MELAS) mtDNA mutation, alone or in combination with the np 12300
suppressor mutation. The mutant tRNA(Leu)(UUR) is aminoacylated very poorl
y or not at all, whereas the suppressor tRNA(Leu)(CUN) is efficiently amino
acylated. Deacylated mitochondrial tRNA(Leu)(CUN) is present, in all human
cells tested, in two structural isoforms that are separable on denaturing g
els, indicating a difference in primary structure. The ratio of the two iso
forms 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 t
RNA(Leu)(CUN) could be a natural suppression mechanism for the np 3243 and
other mitochondrial tRNA(Leu)(UUR) mutations and could underlie some of the
phenotypic variability of np 3243 disease.