Mechanisms of ribosomal fidelity

Currently, we are attempting to expand our understanding of the mechanisms that govern translational fidelity, and its impact on cellular fitness and codon evolution. In particular, we are interested in defining features of the ribosome, mRNA and associated translational factors that are important for the proofreading process that we discovered. Furthermore, while recently there has been much theoretical discussion about the selection pressure imposed by the ribosome on gene evolution and codon context, experimental support for this hypothesis is lacking. We propose that the fidelity of protein synthesis greatly impacts gene expression by affecting translational efficiencies, and hence has been a key factor during codon-choice evolution within an organism. We are beginning to utilize proteomics and genomic approaches to gain a thorough understanding of the proposed intimate relationship between translational fidelity and efficiency. By identifying specific factors that may be regulated by premature termination as a result of ribosomal proofreading, key information about gene regulation and its relation to codon bias rules is likely to be delineated.