Quality control in aminoacyl-tRNA synthesis its role in translational fidelity

Accurate translation of mRNA into protein is vital for maintenance of cellular integrity. Translational fidelity is achieved by two key events: synthesis of correctly paired aminoacyl-tRNAs by aminoacyl-tRNA synthetases (aaRSs) and stringent selection of aminoacyl-tRNAs (aa-tRNAs) by the ribosome. AaRSs define the genetic code by catalyzing the formation of precise aminoacyl ester-linked tRNAs via a two-step reaction. AaRSs ensure faithful aa-tRNA synthesis via high substrate selectivity and/or by proofreading (editing) of noncognate products. About half of the aaRSs rely on proofreading mechanisms to achieve high levels of accuracy in aminoacylation. Editing functions in aaRSs contribute to the overall low error rate in protein synthesis. Over 40 years of research on aaRSs using structural, biochemical, and kinetic approaches has expanded our knowledge of their cellular roles and quality control mechanisms. Here, we review aaRS editing with an emphasis on the mechanistic and kinetic details of the process.