tRNA modification GTPase GTPBP3, mitochondrial is anenzyme that in human is encoded by theGTPBP3gene on chromosome 19.[5][6]
The GTPBP3 gene encodes aGTP-binding protein that is evolutionarily conserved from bacteria to mammals[7] and which is localized to themitochondrion and functions intRNA modification.[6] At least two major isoforms due toalternative splicing are known In addition, apolymorphism onvaline 250 is known and may influence aminoglydoside-induced deafness.[6]
The GTPBP3 gene contains 10 exons,[6] and encodes a ~44 kDaGTP-binding protein that is evolutionarily conserved from bacteria to mammals.[7] The N-terminal domain of mitochondrial tRNA modification GTPase mediates the dimerization of the protein in a potassium-independent manner,[8] which is thought to be related to the construction of the binding site for the one-carbon-unit donor in itstRNA modification reaction function.[8]
Mitochondrial tRNA modification GTPase is thought to catalyze the formation of 5-taurinomethyluridine (τm(5)U) in the anticodon wobble position of five mitochondrial tRNA.[9] The gene was first discovered yeast where the mutation of the yeast homolog of human GTPBP3, MSS1, is found to elicit respiratory defect in yeast only when the mitochondrial 155rRNA P(R)454 is present. The latter is equivalent to the human 12rRNA A1555G mutation which has been found to associate with deafness. Hence GTPBP3 and its yeast homolog function in modification of mitochondrial function. In human, GTPBP3 is ubiquitously expressed in multiple tissues in multiple transcripts.[7] As a tRNA modification enzyme, it is thought to function to modify codon-anticodon interaction, which is consistent with its modification of the severity of phenotypes in 12S rRNA A1555G mutation..
Mutations in GTPBP3 are known to causehypertrophic cardiomyopathy and mitochondrial defects.[9] Individuals withhomozygous orcompound heterozygous mutations in GTPBP3 present with combined deficiency ofrespiratory chain complexes in skeletal muscle,[9] which require mitochondrial translation of mitochondrial-encoded complex subunits to assemble. GTPBP3 mutations cause severe mitochondrial translation defect. The majority of characterized subjects presented withlactic acidosis andhypertrophic cardiomyopathy.
The valine 250 polymorphisms on GTPBP3 is associated with severity of aminoglycoside-induced deafness in human, a disease associated withhomoplasmic A1555G mutation in the mitochondrial-encoded 12S rRNA and is characterized by deafness, varying from profond congenital hearing loss to normal hearing.
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