Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies

Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and s...

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Bibliographic Details
Published in:Nature (London) 1991-05, Vol.351 (6323), p.236-239
Main Authors: Hess, John F, Parisi, Melissa A, Bennett, Jeffrey L, Clayton, David A
Format: Article
Language:English
Subjects:
Base Sequence
Biochemistry
Biological and medical sciences
Blotting, Western
Brain Diseases - genetics
Cellular biology
Chromosome Mapping
DNA Mutational Analysis
DNA, Mitochondrial - genetics
Fibers
Fundamental and applied biological sciences. Psychology
Genetics
Humans
In Vitro Techniques
Mitochondria, Muscle - metabolism
Mitochondrial DNA
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Molecules
Mutagenesis. Repair
Mutation
Peptide Termination Factors - genetics
RNA, Ribosomal - genetics
RNA, Transfer - genetics
Transcription, Genetic
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Summary:Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products.
ISSN:0028-0836
1476-4687
DOI:10.1038/351236a0