CO(2)-sensitive tRNA modification associated with human mitochondrial disease.
CO(2)-sensitive tRNA modification associated with human mitochondrial disease.
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DOI：
10.1038/s41467-018-04250-4
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发表时间：
2018-05-14
影响因子：
16.6
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Lin H;Miyauchi K;Harada T;Okita R;Takeshita E;Komaki H;Fujioka K;Yagasaki H;Goto YI;Yanaka K;Nakagawa S;Sakaguchi Y;Suzuki T
一般认为，tRNA修饰是稳定和静态的，其频率很少受到调节。N6-苏氨酰氨甲酰基腺苷（t6 A）出现在5种线粒体（mt-）tRNA的37位。我们表明，YRDC和OSGEPL 1负责t6 A37的形成，利用L-苏氨酸，ATP和CO2/碳酸氢盐作为底物。OSGEPL 1敲除细胞表现出呼吸缺陷和线粒体翻译减少。我们发现从MERRF样患者细胞中分离的突变型mt-tRNA中t6 A37水平较低，表明缺乏t6 A37导致病理后果。t6 A37形成的动力学测量显示，二氧化碳/碳酸氢盐的Km值非常高（31 mM），表明二氧化碳/碳酸氢盐是t6 A37形成的限速因素。与此相一致，我们观察到从无碳酸氢盐培养的人细胞中分离的mt-tRNA中t6 A37的频率较低。这些发现表明，t6 A37是通过感知细胞内CO2/碳酸氢盐浓度来调节的，这意味着线粒体翻译在生理条件下以密码子特异性方式进行调节。转运RNA修饰在蛋白质合成中起关键作用。在这里，作者揭示了t6 A37 tRNA修饰是通过感知线粒体中细胞内CO2浓度来动态调节的，这意味着蛋白质合成的代谢调节。
It has been generally thought that tRNA modifications are stable and static, and their frequencies are rarely regulated. N6-threonylcarbamoyladenosine (t6A) occurs at position 37 of five mitochondrial (mt-)tRNA species. We show that YRDC and OSGEPL1 are responsible for t6A37 formation, utilizing L-threonine, ATP, and CO2/bicarbonate as substrates. OSGEPL1-knockout cells exhibit respiratory defects and reduced mitochondrial translation. We find low level of t6A37 in mutant mt-tRNA isolated from the MERRF-like patient’s cells, indicating that lack of t6A37 results in pathological consequences. Kinetic measurements of t6A37 formation reveal that the Km value of CO2/bicarbonate is extremely high (31 mM), suggesting that CO2/bicarbonate is a rate-limiting factor for t6A37 formation. Consistent with this, we observe a low frequency of t6A37 in mt-tRNAs isolated from human cells cultured without bicarbonate. These findings indicate that t6A37 is regulated by sensing intracellular CO2/bicarbonate concentration, implying that mitochondrial translation is modulated in a codon-specific manner under physiological conditions. Transfer RNA modifications play critical roles in protein synthesis. Here the authors reveal the t6A37 tRNA modification is dynamically regulated by sensing intracellular CO2 concentration in mitochondria, implying metabolic regulation of protein synthesis.
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影响因子：
14.9
作者：
Kimura S;Miyauchi K;Ikeuchi Y;Thiaville PC;Crécy-Lagard Vd;Suzuki T
通讯作者：
Suzuki T
DOI：
10.1007/978-94-007-7359-2_11
发表时间：
2014-01-01
期刊：
CARBONIC ANHYDRASE: MECHANISM, REGULATION, LINKS TO DISEASE, AND INDUSTRIAL APPLICATIONS
影响因子：
--
作者：
Benej, Martin;Pastorekova, Silvia;Pastorek, Jaromir
通讯作者：
Pastorek, Jaromir
Wolf Psort：蛋白质定位预测因子。
影响因子：
14.9
作者：
Horton, Paul;Park, Keun-Joon;Obayashi, Takeshi;Fujita, Naoya;Harada, Hajime;Adams-Collier, C J;Nakai, Kenta
通讯作者：
Nakai, Kenta
影响因子：
14.9
作者：
Jühling F;Mörl M;Hartmann RK;Sprinzl M;Stadler PF;Pütz J
通讯作者：
Pütz J
影响因子：
14.9
作者：
Kang BI;Miyauchi K;Matuszewski M;D'Almeida GS;Rubio MAT;Alfonzo JD;Inoue K;Sakaguchi Y;Suzuki T;Sochacka E;Suzuki T
通讯作者：
Suzuki T