Characterization of the human mitochondrial Arginyl-tRNA synthetase and contribution to the général understanding of pathologies linked to mutations on mitochondrial aminoacyl-tRNA synthetases

Abstract : Human mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are housekeeping enzymes involved in the mitochondrial translation. They catalyze the aminoacylation of tRNAs with their cognate amino acids. Mutations in their nuclear genes are correlated with pathologies with a broad spectrum of clinical phenotypes, but with so far no clear explanations about the underlying molecular mechanism(s). The aim of this PhD work follows the long-standing efforts of the host laboratory but expand the interest and knowledge to an unexplored system: the human mitochondrial arginyl-tRNA synthetase (mt-ArgRS). Mutations in the mt-ArgRS lead to Pontocebellar hypoplasia type 6, a severe neuro-developmental pathology. I thus contributed to i) comprehensively analyze the clinical data reported in pathologies related to mutations on mt-aaRSs, resulting in a categorization according to the affected anatomical system; ii) decipher some cellular properties of the mt-ArgRS; and iii) investigate to impact of disease-associated mutations on mt-aaRSs properties. Combined with previous works, the present results expand the knowledge of the mt-aaRSs, shedding new light on the link between mt-aaRSs-mutations and disease.
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Ligia Elena Gonzalez Serrano. Characterization of the human mitochondrial Arginyl-tRNA synthetase and contribution to the général understanding of pathologies linked to mutations on mitochondrial aminoacyl-tRNA synthetases. Cellular Biology. Université de Strasbourg, 2018. English. ⟨NNT : 2018STRAJ074⟩. ⟨tel-02285436⟩

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