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

研究成果: Article査読

42 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1565-1583
ページ数19
ジャーナルNucleic acids research
46
4
DOI
出版ステータスPublished - 2018 2 28
外部発表はい

ASJC Scopus subject areas

  • 遺伝学

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