Isolation and Characterization of the Putative Nuclear Modifier Gene MTO1 Involved in the Pathogenesis of Deafness-associated Mitochondrial 12 S rRNA A1555G Mutation

• Published in: The Journal of biological chemistry Vol. 277; no. 30; pp. 27256 - 27264
• Main Authors: Li, Xiaoming, Li, Ronghua, Lin, Xinhua, Guan, Min-Xin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2002; American Society for Biochemistry and Molecular Biology
• Subjects: Alleles; Alternative Splicing; Amino Acid Sequence; Carrier Proteins - metabolism; Cloning, Molecular; DNA, Complementary - metabolism; Exons; Expressed Sequence Tags; Genetic Complementation Test; Glucose - pharmacology; Glycerol - pharmacology; Humans; Introns; Microscopy, Fluorescence; Mitochondria - metabolism; Mitochondrial Proteins; Models, Genetic; Molecular Sequence Data; Mutation; Phenotype; Protein Structure, Secondary; Reverse Transcriptase Polymerase Chain Reaction; RNA, Ribosomal - metabolism; RNA, Transfer - metabolism; RNA-Binding Proteins; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Tissue Distribution; Transfection; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M203267200

The human mitochondrial 12 S rRNA A1555G mutation has been found to be associated with aminoglycoside-induced and non-syndromic deafness. However, putative nuclear modifier gene(s) have been proposed to regulate the phenotypic expression of this mutation. In yeast, the mutant alleles of MTO1, encoding a mitochondrial protein, manifest respiratory-deficient phenotype only when coupled with the mitochondrial 15 S rRNA PR454 mutation corresponding to human A1555G mutation. This suggests that the MTO1-like modifier gene may influence the phenotypic expression of human A1555G mutation. Here we report the identification of full-length cDNA and elucidation of genomic organization of the human MTO1 homolog. Human Mto1 is an evolutionarily conserved protein that implicates a role in the mitochondrial tRNA modification. Functional conservation of this protein is supported by the observation that isolated humanMTO1 cDNA can complement the respiratory deficient phenotype of yeast mto1 cells carrying PR454 mutation. MTO1 is ubiquitously expressed in various tissues, but with a markedly elevated expression in tissues of high metabolic rates including cochlea. These observations suggest that human MTO1 is a structural and functional homolog of yeast MTO1. Thus, it may play an important role in the pathogenesis of deafness-associated A1555G mutation in 12 S rRNA gene or mutations in tRNA genes.