Department of Biochemistry & Biophysics
Center for RNA Biology
Host: John Hunt
Title: Translation of the Genetic Code: Brakes included
Abstract: Translation of the genetic code from mRNA into protein ultimately determines the protein composition of the cell. In all three kingdoms, the rate and efficiency of translation elongation are modulated by the particular choice of synonymous codons, although synonymous codons specify insertion of the same amino acid. The problem of how codon choice affects translation is central to biology, but has been difficult to study, in part because the identities of the codons or codon combinations that result in decreased translation efficiency have been largely unknown, particularly in eukaryotes. To this end, we initially performed a systematic analysis to identify codon repeats that cause decreased translation efficiency in the yeast Saccharomyces cerevisiae, finding that Arg CGA codons are translated extremely inefficiently, due to I·A wobble decoding. Furthermore, adjacent CGA-CGA codons (codon pairs) are far more inhibitory than isolated CGA codons, implying that other inhibitory pairs composed of non-identical codons exist. We then proceeded to identify 16 additional strongly inhibitory codon pairs, most of which are translated very slowly in native yeast transcripts, substantiating the idea that inefficient translation is related to slow translation.
I will discuss current efforts to address two issues: the functional importance of inhibitory codon pairs and the mechanisms by which cells prevent aberrant translation at these pairs.