Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote.
Translational fidelity maintenance preventing Ser mis-incorporation at Thr codon in protein from eukaryote.
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DOI：
10.1093/nar/gks982
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发表时间：
2013-01-07
影响因子：
14.9
通讯作者：
Wang ED
中科院分区：
文献类型：
--
作者：
Zhou XL;Ruan ZR;Huang Q;Tan M;Wang ED
氨酰-tRNA合成酶（阿尔斯）催化蛋白质合成的第一步，产生氨酰-tRNA作为结构单元。真核阿尔斯在末端延伸或插入方面不同于其原核对应物。此外，aaRS的编辑功能是排除给定密码子处的非同源氨基酸并确保整体翻译保真度的不可或缺的检查点。我们发现高等真核生物编码两种胞质型苏氨酰-tRNA合成酶（ThrRSs），它们的N端不同。较长的同种型与高等真核生物的ThrRS比与低等真核生物的ThrRS更密切相关。产生酵母菌株以包括编码ThrRS的thrS基因的缺失。结合体外生化和体内遗传学数据，系统分析了真核细胞质ThrRS，阐明了真核细胞质ThrRS特异性N端延伸的作用。进一步阐明了酿酒酵母ThrRS（ScThrRS）介导的氨酰化和编辑活性的机制。有趣的是，即使在显著的环境压力下，酵母细胞也能耐受ScThrRS编辑活性位点的变异，而蛋白质组中没有显著的Thr至Ser转化，这意味着氨酰化下游的检查点为酵母翻译系统提供了进一步的质量控制机制。本研究首次全面阐明了真核ThrRS的翻译保真度控制机制。
Aminoacyl-tRNA synthetase (aaRS) catalyzes the first step of protein synthesis, producing aminoacyl-tRNAs as building blocks. Eukaryotic aaRS differs from its prokaryotic counterpart in terminal extension or insertion. Moreover, the editing function of aaRSs is an indispensable checkpoint excluding non-cognate amino acids at a given codon and ensuring overall translational fidelity. We found higher eukaryotes encode two cytoplasmic threonyl-tRNA synthetases (ThrRSs) with difference in N-terminus. The longer isoform is more closely related to the ThrRSs of higher eukaryotes than to those of lower eukaryotes. A yeast strain was generated to include deletion of the thrS gene encoding ThrRS. Combining in vitro biochemical and in vivo genetic data, ThrRSs from eukaryotic cytoplasm were systematically analyzed, and role of the eukaryotic cytoplasmic ThrRS-specific N-terminal extension was elucidated. Furthermore, the mechanisms of aminoacylation and editing activity mediated by Saccharomyces cerevisiae ThrRS (ScThrRS) were clarified. Interestingly, yeast cells were tolerant of variation at the editing active sites of ScThrRS without significant Thr-to-Ser conversion in the proteome even under significant environmental stress, implying checkpoints downstream of aminoacylation to provide a further quality control mechanism for the yeast translation system. This study has provided the first comprehensive elucidation of the translational fidelity control mechanism of eukaryotic ThrRS.
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影响因子：
4.8
作者：
Nangle, LA;Lagardt, VD;Schimmel, P
通讯作者：
Schimmel, P
影响因子：
--
作者：
Nangle, Leslie A.;Motta, Candace M.;Schimmel, Paul
通讯作者：
Schimmel, Paul
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.
影响因子：
4.8
作者：
Dulic, Morana;Cvetesic, Nevena;Gruic-Sovulj, Ita
通讯作者：
Gruic-Sovulj, Ita
DOI：
10.1073/pnas.87.10.3665
发表时间：
1990-05-01
影响因子：
11.1
作者：
SIVARAM, P;DEUTSCHER, MP
通讯作者：
DEUTSCHER, MP