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Mitochondrial deafness alleles confer misreading of the genetic code


Hobbie, S N; Bruell, C M; Akshay, S; Kalapala, S K; Shcherbakov, D; Böttger, E C (2008). Mitochondrial deafness alleles confer misreading of the genetic code. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 105(9):3244-3249.

Abstract

Despite the fact that important genetic diseases are caused by mutant mitochondrial ribosomes, the molecular mechanisms by which such ribosomes result in a clinical phenotype remain largely unknown. The absence of experimental models for mitochondrial diseases has also prevented the rational search for therapeutic interventions. Here, we report on the construction of bacterial hybrid ribosomes that contain various versions of the mitochondrial decoding region of ribosomal RNA. We show that the pathogenic mutations A1555G and C1494T decrease the accuracy of translation and render the ribosomal decoding site hypersusceptible to aminoglycoside antibiotics. This finding suggests misreading of the genetic code as an important molecular mechanism in disease pathogenesis.

Despite the fact that important genetic diseases are caused by mutant mitochondrial ribosomes, the molecular mechanisms by which such ribosomes result in a clinical phenotype remain largely unknown. The absence of experimental models for mitochondrial diseases has also prevented the rational search for therapeutic interventions. Here, we report on the construction of bacterial hybrid ribosomes that contain various versions of the mitochondrial decoding region of ribosomal RNA. We show that the pathogenic mutations A1555G and C1494T decrease the accuracy of translation and render the ribosomal decoding site hypersusceptible to aminoglycoside antibiotics. This finding suggests misreading of the genetic code as an important molecular mechanism in disease pathogenesis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:10 Nov 2008 13:07
Last Modified:05 Apr 2016 12:29
Publisher:National Academy of Sciences
ISSN:0027-8424
Additional Information:Copyright: National Academy of Sciences USA
Publisher DOI:10.1073/pnas.0707265105
PubMed ID:18308926
Permanent URL: http://doi.org/10.5167/uzh-4261

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