Mitochondrial deafness alleles confer misreading of the genetic code

被引:90
作者
Hobbie, Sven N. [1 ]
Bruell, Christian M. [1 ]
Akshay, Subramanian [1 ]
Kalapala, Sarath K. [1 ]
Shcherbakov, Dmitry [1 ]
Boettger, Erik C. [1 ]
机构
[1] Univ Zurich, Inst Med Mikrobiol, CH-8006 Zurich, Switzerland
关键词
decoding; mitochondria; mutant rRNA; ribosomes; disease;
D O I
10.1073/pnas.0707265105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:3244 / 3249
页数:6
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