UCLA

Cells maintain fidelity in protein synthesis through various mechanisms including aminoacyl-tRNA synthetases (aaRSs) that are able to discriminate tRNAs and their cognate amino acids. Substrate specificity along with editing functions of aaRSs act to prevent or remove incorrect amino acids charged onto tRNAs. Editing domains are highly conserved and found in both prokaryotes and eukaryotes; knocking out the editing function of an aaRS does not seem to affect cell viability. To determine the biological relevance of the editing domains found on aaRSs, it is essential to determine the contribution of editing to protein fidelity in vivo. Bacillus subtilis serves as an ideal model to study this phenomenon because it possesses a small gene-enocoded, 10 amino acid pheromone peptide, ComX. ComX is processed, modified, and secreted by B. subtilis as a signaling molecule that can easily be purified. The amino acid sequence of ComX can be altered to some degree while maintaining cellular activity enabling different strains that produce variants of ComX pheromone to be compared for levels of mistranslation. Ultimately future experiments will reveal the impact that editing by an aaRS has on the fidelity of protein synthesis in vivo by quantifying the rates of mistranslation in strains of B. subtilis that express an editing-defective tRNA synthetase and comparing it to levels of mistranslation to wild type strains.