Research Projects

Role of the genetic code in translation in S. cerevisiae

The genetic code and protein synthesis.

The major focus in the laboratory is to understand how codon choice influences translation efficiency in a eukaryote. Although codon choice has been associated with large disparities in translation efficiency for many years, it is still unknown the extent to which codon choice directly influences translation efficiency, as well as the identity and properties of the codon-initiated signals. We think codon-mediated regulation of expression is likely to be functionally important and nearly universal, as all organisms require wobble decoding of some codons and since clusters of rare codons are frequently conserved between orthologous genes in humans and chimps. Two ongoing projects are described below.

Define the identity and properties of inhibitory codon combinations

Although accurate and efficient translation of mRNA into proteins is crucially important for the cell, not all of the 61 codons that specify insertion of amino acids into nascent polypeptides behave equally in this process. In fact, almost all synonymous codons, i.e. those that specify the same amino acid, are used at very different frequencies within most organisms, including the yeast S. cerevisiae.

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Determine the mechanisms by with inhibitory codons exert their effects

A second project on codon-mediated inhibition is aimed at deducing the mechanism(s) by which inhibitory codons exert their effects on translation. Our analysis with CGA codons suggests that profound differences in translation efficiency can stem directly from decoding interactions in the ribosome. Thus, the study of codon-mediated inhibition is likely to provide insights into the workings of the ribosome, the RNA-protein machine responsible for converting genetic information into proteins, and possibly into mechanisms of ribosomal quality control.

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