Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease

Kana Asano, Takeo Suzuki, Ayaka Saito, Fan Yan Wei, Yoshiho Ikeuchi, Tomoyuki Numata, Ryou Tanaka, Yoshihisa Yamane, Takeshi Yamamoto, Takanobu Goto, Yoshihito Kishita, Kei Murayama, Akira Ohtake, Yasushi Okazaki, Kazuhito Tomizawa, Yuriko Sakaguchi, Tsutomu Suzuki

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Modified uridine containing taurine, 5-taurinometh yluridine (m5U), is found at the anticodon first position of mitochondrial (mt-)transfer RNAs (tRNAs). Previously, we reported that m5U is absent in mt-tRNAs with pathogenic mutations associated with mitochondrial diseases. However, biogenesis and physiological role of m5U remained elusive. Here, we elucidated m5U biogenesis by confirming that 5,10-methylene-tetrahydrofolate and taurine are metabolic substrates for m5U formation catalyzed by MTO1 and GTPBP3. GTPBP3-knockout cells exhibited respiratory defects and reduced mitochondrial translation. Very little m5U34 was detected in patient's cells with the GTPBP3 mutation, demonstrating that lack of m5U results in pathological consequences. Taurine starvation resulted in downregulation of m5U frequency in cultured cells and animal tissues (cat liver and flatfish). Strikingly, 5-carboxymethylaminomethyluridine (cmnm5U), in which the taurine moiety of m5U is replaced with glycine, was detected in mt-tRNAs from taurinedepleted cells. These results indicate that tRNA modifications are dynamically regulated via sensing of intracellular metabolites under physiological condition.

Original languageEnglish
Pages (from-to)1565-1583
Number of pages19
JournalNucleic acids research
Volume46
Issue number4
DOIs
Publication statusPublished - 2018 Feb 28
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Asano, K., Suzuki, T., Saito, A., Wei, F. Y., Ikeuchi, Y., Numata, T., Tanaka, R., Yamane, Y., Yamamoto, T., Goto, T., Kishita, Y., Murayama, K., Ohtake, A., Okazaki, Y., Tomizawa, K., Sakaguchi, Y., & Suzuki, T. (2018). Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. Nucleic acids research, 46(4), 1565-1583. https://doi.org/10.1093/nar/gky068