Resampling and Editing of Mischarged tRNA Prior to Translation Elongation
Resampling and Editing of Mischarged tRNA Prior to Translation Elongation
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DOI：
10.1016/j.molcel.2009.01.031
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发表时间：
2009-03-13
期刊：
影响因子：
16
通讯作者：
Ibba, Michael
中科院分区：
文献类型：
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作者：
Ling, Jiqiang;So, Byung Ran;Ibba, Michael
遗传密码的忠实翻译依赖于GTMEEF-Tu将正确带电的氨酰-tRNA递送到核糖体以与同源密码子配对。通过底物特异性和产物编辑的组合，通过氨酰-tRNA合成酶实现同源氨基酸和tRNA的精确偶联。一旦被氨酰-tRNA合成酶释放，同源和近同源氨酰-tRNA都被认为是通过与EF-Tu的结合而致力于核糖体蛋白质合成。在这里，我们表明，氨酰-tRNA与EF-Tu中心点GTP的三元复合物可以很容易地解离和重新结合氨酰-tRNA合成酶。对于带错电荷的物种，这允许通过产物编辑途径进行重新定位，从而降低氨酰-tRNA合成的总体错误率。在体外蛋白质合成过程中，错误电荷的tRNA的恢复显示出将翻译的准确性提高了十倍以上，这支持了在翻译延伸之前存在额外的质量控制步骤。
Faithful translation of the genetic code depends on the GTPase EF-Tu delivering correctly charged aminoacyl-tRNAs to the ribosome for pairing with cognate codons. The accurate coupling of cognate amino acids and tRNAs by the aminoacyl-tRNA synthetases is achieved through a combination of substrate specificity and product editing. Once released by aminoacyl-tRNA synthetases, both cognate and near-cognate aminoacyl-tRNAs were considered to be committed to ribosomal protein synthesis through their association with EF-Tu. Here we show instead that aminoacyl-tRNAs in ternary complex with EF-Tu center dot GTP can readily dissociate and rebind to aminoacyl-tRNA synthetases. For mischarged species, this allows resampling by the product editing pathway, leading to a reduction in the overall error rate of aminoacyl-tRNA synthesis. Resampling of mischarged tRNAs was shown to increase the accuracy of translation over ten fold during in vitro protein synthesis, supporting the presence of an additional quality control step prior to translation elongation.