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

Stable Identifier
R-HSA-6787403
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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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. 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
25552653 MTO1 mediates tissue specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention

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

Hum. Mol. Genet. 2015
12456664 Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases

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

EMBO J. 2002
23929671 MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast

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

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

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

Am. J. Hum. Genet. 2012
Participants
Participant Of
Event Information
Catalyst Activity
Catalyst Activity
Title
transferase activity of MTO1 [mitochondrial matrix]
Physical Entity
Activity
Title
transferase activity of GTPBP3 [mitochondrial matrix]
Physical Entity
Activity
Inferred From
Authored
Reviewed
Created