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•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.
Ling, J., So, B.R., Yadavalli, S.S., Roy, H., Shoji, S., Fredrick, K., Musier-Forsyth, K. and Ibba, M. (2009) Resampling and editing of mischarged tRNA prior to translation elongation. Mol. Cell 33, 654-660. https://doi.org10.1016/j.molcel.2009.01.031
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NOTICE: this is the author’s version of a work that was accepted for publication in Molecular Cell. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular Cell, volume 33, in 2009. https://doi.org/10.1016/j.molcel.2009.01.031
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