Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability
Elucidation of tRNA-dependent editing by a class II tRNA synthetase and significance for cell viability
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DOI：
10.1093/emboj/cdg065
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发表时间：
2003-02-03
期刊：
影响因子：
11.4
通讯作者：
Schimmel, P
中科院分区：
文献类型：
--
作者：
Beebe, K;de Pouplana, LR;Schimmel, P
由I类tRNA合成酶编辑错误激活的氨基酸由I类酶特异性的专门内部结构域编码。相比之下，很少有人知道结构不同的II类酶的编辑活动。在这里，我们表明，II类丙氨酰-tRNA合成酶（AlaRS）有一个专门的内部结构域，似乎弱相关的附加结构域的苏氨酰-tRNA合成酶（ThrRS），但不相关的发现在I类酶。错误激活的甘氨酸或丝氨酸的编辑被证明需要tRNA辅因子。上述结构域中的特定突变破坏编辑并导致产生错误的tRNA。这类特异性编辑域被发现是必不可少的细胞生长，在存在浓度升高的甘氨酸或丝氨酸。与ThrRS相反，ThrRS的编辑结构域在所有三个生物界中都没有发现，它很早就被纳入AlaRS，并在整个进化过程中存在。因此，AlaRS的tRNA依赖性编辑可能对于使遗传密码足够准确以生成生命树至关重要。
Editing of misactivated amino acids by class I tRNA synthetases is encoded by a specialized internal domain specific to class I enzymes. In contrast, little is known about editing activities of the structurally distinct class II enzymes. Here we show that the class II alanyl-tRNA synthetase (AlaRS) has a specialized internal domain that appears weakly related to an appended domain of threonyl-tRNA synthetase (ThrRS), but is unrelated to that found in class I enzymes. Editing of misactivated glycine or serine was shown to require a tRNA cofactor. Specific mutations in the aforementioned domain disrupt editing and lead to production of mischarged tRNA. This classspecific editing domain was found to be essential for cell growth, in the presence of elevated concentrations of glycine or serine. In contrast to ThrRS, where the editing domain is not found in all three kingdoms of living organisms, it was incorporated early into AlaRSs and is present throughout evolution. Thus, tRNA-dependent editing by AlaRS may have been critical for making the genetic code sufficiently accurate to generate the tree of life.