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.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 1565-1583 |
| ページ数 | 19 |
| ジャーナル | Nucleic acids research |
| 巻 | 46 |
| 発行部数 | 4 |
| DOI | |
| 出版物ステータス | 出版済み - 2 28 2018 |
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All Science Journal Classification (ASJC) codes
- Genetics
これを引用
Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. / Asano, Kana; Suzuki, Takeo; Saito, Ayaka; Wei, Fan Yan; Ikeuchi, Yoshiho; Numata, Tomoyuki; Tanaka, Ryou; Yamane, Yoshihisa; Yamamoto, Takeshi; Goto, Takanobu; Kishita, Yoshihito; Murayama, Kei; Ohtake, Akira; Okazaki, Yasushi; Tomizawa, Kazuhito; Sakaguchi, Yuriko; Suzuki, Tsutomu.
：: Nucleic acids research, 巻 46, 番号 4, 28.02.2018, p. 1565-1583.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease
AU - Asano, Kana
AU - Suzuki, Takeo
AU - Saito, Ayaka
AU - Wei, Fan Yan
AU - Ikeuchi, Yoshiho
AU - Numata, Tomoyuki
AU - Tanaka, Ryou
AU - Yamane, Yoshihisa
AU - Yamamoto, Takeshi
AU - Goto, Takanobu
AU - Kishita, Yoshihito
AU - Murayama, Kei
AU - Ohtake, Akira
AU - Okazaki, Yasushi
AU - Tomizawa, Kazuhito
AU - Sakaguchi, Yuriko
AU - Suzuki, Tsutomu
PY - 2018/2/28
Y1 - 2018/2/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85043264679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043264679&partnerID=8YFLogxK
U2 - 10.1093/nar/gky068
DO - 10.1093/nar/gky068
M3 - Article
AN - SCOPUS:85043264679
VL - 46
SP - 1565
EP - 1583
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 4
ER -