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
リソース情報
ヒト・動物細胞 CHO-K1