論文 - 詳細
| RRC ID | 52583 |
|---|---|
| 著者 | Asano K, Suzuki T, Saito A, Wei FY, 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. |
| タイトル | Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Modified uridine containing taurine, 5-taurinomethyluridine (τm5U), is found at the anticodon first position of mitochondrial (mt-)transfer RNAs (tRNAs). Previously, we reported that τm5U is absent in mt-tRNAs with pathogenic mutations associated with mitochondrial diseases. However, biogenesis and physiological role of τm5U remained elusive. Here, we elucidated τm5U biogenesis by confirming that 5,10-methylene-tetrahydrofolate and taurine are metabolic substrates for τm5U formation catalyzed by MTO1 and GTPBP3. GTPBP3-knockout cells exhibited respiratory defects and reduced mitochondrial translation. Very little τm5U34 was detected in patient's cells with the GTPBP3 mutation, demonstrating that lack of τm5U results in pathological consequences. Taurine starvation resulted in downregulation of τm5U frequency in cultured cells and animal tissues (cat liver and flatfish). Strikingly, 5-carboxymethylaminomethyluridine (cmnm5U), in which the taurine moiety of τm5U is replaced with glycine, was detected in mt-tRNAs from taurine-depleted cells. These results indicate that tRNA modifications are dynamically regulated via sensing of intracellular metabolites under physiological condition. |
| 巻・号 | 46(4) |
| ページ | 1565-1583 |
| 公開日 | 2018-2-28 |
| DOI | 10.1093/nar/gky068 |
| PII | 4829701 |
| PMID | 29390138 |
| PMC | PMC5829720 |
| MeSH | Animals Carrier Proteins / physiology Cats Child, Preschool Female GTP-Binding Proteins / genetics GTP-Binding Proteins / physiology HEK293 Cells HeLa Cells Humans Mitochondria / metabolism Mitochondrial Diseases / genetics RNA, Transfer / chemistry RNA, Transfer / metabolism* RNA-Binding Proteins Taurine / deficiency* Uridine / analogs & derivatives* Uridine / biosynthesis |
| IF | 11.502 |
| 引用数 | 32 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | CHO-K1 |