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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MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Wimberly B.T.
Brodersen D.E.
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MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Brodersen D.E.
Clemons Jr. W.M.
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MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Department of Biochemistry, Univ. of Utah School of Medicine, Salt Lake CityMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Clemons Jr. W.M.
Morgan-Warren R.J.
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MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Morgan-Warren R.J.
Carter A.P.
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MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Carter A.P.
Vonrheln C.
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Global Phasing Ltd., Sheraton House, Cambridge CB3 0AX, Castle ParkMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Vonrheln C.
Hartsch T.
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Göttingen Genomics Laboratory, Inst. F. Mikrobiologie und Genetik, Georg-August-Univ. Göttingen, D-37077 GöttingenMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Hartsch T.
Ramakrishnan V.
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MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
机构:
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Wimberly B.T.
Brodersen D.E.
论文数: 0引用数: 0
h-index: 0
机构:
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Brodersen D.E.
Clemons Jr. W.M.
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h-index: 0
机构:
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Department of Biochemistry, Univ. of Utah School of Medicine, Salt Lake CityMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Clemons Jr. W.M.
Morgan-Warren R.J.
论文数: 0引用数: 0
h-index: 0
机构:
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Morgan-Warren R.J.
Carter A.P.
论文数: 0引用数: 0
h-index: 0
机构:
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Carter A.P.
Vonrheln C.
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h-index: 0
机构:
Global Phasing Ltd., Sheraton House, Cambridge CB3 0AX, Castle ParkMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Vonrheln C.
Hartsch T.
论文数: 0引用数: 0
h-index: 0
机构:
Göttingen Genomics Laboratory, Inst. F. Mikrobiologie und Genetik, Georg-August-Univ. Göttingen, D-37077 GöttingenMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
Hartsch T.
Ramakrishnan V.
论文数: 0引用数: 0
h-index: 0
机构:
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills RoadMRC Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road