Translation of the genetic code from triplet codons in mRNAs into the amino acids in proteins determines the protein composition in the cell. The translation process influences the amount of each protein, the errors within each protein, as well as programmed deviations that affect the protein sequence. Although accurate and efficient translation of mRNA into proteins is crucially important for the cell, there are substantial differences in translation caused by the choice of synonymous codons used to encode a polypeptide. Synonymous codons specify insertion of the identical amino acid, but differ from each other in the amounts of tRNA available to decode the codon as well as the need for wobble base pairing between the codon and the anticodon of the tRNA.
The goal of research in the Grayhack laboratory is to define the rules and mechanisms by which specific arrangements of codons impair translation in the yeast Saccharomyces cerevisiae, and to identify regulatory models dictated by codon usage in the yeast genome. Although codon use has been implicated as a determinant of expression levels, neither the identity, nor the defining characteristics of codons that impair expression are known. We demonstrated that translation of CGA codon pairs is remarkably inefficient due to wobble decoding, which implicated interactions between sites in the ribosome and the ribosome decoding process as mediators of translation efficiency. We are currently examining the mechanisms by which CGA codon pairs modulate translation and defining novel codon combinations that reduce translation efficiency.