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.

中文翻译：

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与牛磺酸缺乏和人类疾病相关的tRNA修饰的代谢和化学调控

改性的含尿苷牛磺酸，5- taurinomethyluridine（τM ⁵ U），在线粒体（MT-）转运RNA（tRNA的）的反密码子的第一位置中。此前，我们报道了τM ⁵ U是在MT-tRNA的与线粒体疾病相关的基因突变致病缺席。然而，生源和τM的生理作用⁵ ü仍然难以捉摸。在这里，我们阐述τM ⁵通过确认5,10-亚甲基-四氢叶酸和牛磺酸是τM代谢底物生物合成ü ⁵ ü形成由MTO1和GTPBP3催化。GTPBP3-敲除细胞表现出呼吸缺陷和线粒体翻译减少。很少τM ⁵U34在病人对细胞中检测GTPBP3突变，表明缺乏τM的⁵ ü导致病理后果。牛磺酸饥饿导致τM的下调⁵在培养的细胞和动物组织（肝猫和比目鱼）U频率。引人注目的是，5-carboxymethylaminomethyluridine（cmnm ⁵ U），其中τM的牛磺酸部分⁵ U被替换为甘氨酸，在MT-tRNA的检测从牛磺酸缺失的细胞。这些结果表明，在生理条件下通过感测细胞内代谢物可动态调节tRNA修饰。