GTPBP3 and MTO1 transform uridine-34 yielding 5-taurinomethyluridine-34 in tRNA

Stable Identifier
Reaction [omitted]
Homo sapiens
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A conserved pathway consisting of at least GTPBP3 (MSS1 in Saccharomyces cerevisiae, MnmE in Escherichia coli) and MTO1 (MTO1 in S. cerevisiae, MnmG in E. coli) modifies the wobble nucleotide uridine-34 in mitochondrial tRNA (Asano et al. 2018). In humans a methyl group and a taurine group (2-aminoethylsulfonic acid) are conjugated to the 5 position of the uracil ring (Suzuki et al. 2002). In yeast and E. coli a methyl group and a glycine group are conjugated, yielding 5-carboxymethylaminomethyluridine. The details of the reaction mechanism are unknown. Modification of the wobble nucleotide is required for efficient and accurate translation. Mutations in constituents of the pathway cause disease symptoms characteristic of mitochondrial dysfunction: lactic acidosis, hypertrophic cardiomyopathy, respiratory chain defect, and, in association with the A1555G mutation in 12S rRNA, deafness (Ghezzi et al. 2012, Baruffini et al. 2013, Tischner et al. 2015).

Literature References
PubMed ID Title Journal Year
12456664 Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases

Suzuki, T, Suzuki, T, Saigo, K, Watanabe, K, Wada, T

EMBO J. 2002
25552653 MTO1 mediates tissue specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention

Wulff, V, Hofer, A, Wenz, T, Datta, AN, Kremer, L, Tischner, C, Sperl, W, Wurst, W, Dumitru, I, Chrzanowska-Lightowlers, ZM, Stepek, J, Becker, L, De Angelis, MH, Haack, T, Floss, T, Klopstock, T, Prokisch, H

Hum. Mol. Genet. 2015
29390138 Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease

Tanaka, R, Yamane, Y, Goto, T, Wei, FY, Okazaki, Y, Kishita, Y, Asano, K, Saito, A, Ohtake, A, Suzuki, T, Suzuki, T, Numata, T, Murayama, K, Yamamoto, T, Sakaguchi, Y, Tomizawa, K, Ikeuchi, Y

Nucleic Acids Res. 2018
23929671 MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast

Taylor, RW, Dallabona, C, Burlina, A, Yarham, JW, Kopajtich, R, Santra, S, Walther, A, Zeviani, M, Melchionda, L, Ferrero, I, Blakely, EL, Roper, HP, Haack, TB, Vijayaraghavan, S, Lamantea, E, Invernizzi, F, Baruffini, E, Ghezzi, D, Prokisch, H, Donnini, C, Strom, TM

Hum. Mutat. 2013
22608499 Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis

Meitinger, T, Dallabona, C, Burlina, AB, Zeviani, M, Melchionda, L, Ferrero, I, Haack, TB, Parini, R, Invernizzi, F, Baruffini, E, Prokisch, H, Ghezzi, D, Strom, TM

Am. J. Hum. Genet. 2012
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