The Role of Aminoacyl-tRNA Synthesis In Translational Quality Control

Ohio State University Research Foundation -Do Not Use, Columbus OH

Investigators

Abstract

The correct functioning of living systems requires maintaining a certain level of fidelity in all processes dealing with the transfer of information. Translation is the process by which genetic information is transferred from a nucleic acid sequence into the amino acid sequence of a protein. The fidelity of translation is determined at two major points: the accuracy of aminoacyl-tRNA selection by the ribosomes and synthesis of cognate amino acid/tRNA pairs by aminoacyl-tRNA synthetases (aaRS) in the course of the aminoacylation reaction. The aaRSs define the genetic code by pairing tRNAs with the corresponding amino acids. Accurate aminoacyl-tRNA synthesis often involves an additional editing activity intrinsic to many aaRSs. The editing activity significantly decreases the level of mistakes in aminoacyl-tRNA synthesis in vitro and in vivo, although quantitative analysis of its contribution to the overall fidelity of translation has not been performed. The overall aim of this project is to develop experimental systems to quantitatively measure the frequency of aaRS-dependent misincorporation for several amino acids and evaluate the contribution of aaRS editing to overall translational fidelity. The intellectual merits of this research are in achieving significant progress in understanding fundamental biological problems, namely fidelity control in general and the editing mechanisms employed during translation in particular. The broader impacts resulting from the project will be to provide integrated laboratory research and training programs for both undergraduate and graduate students and to establish a new collaborative network.