Identi®cation of stop codon readthrough genes in Saccharomyces cerevisiae

We speci®cally sought genes within the yeast genome controlled by a non-conventional transla-tion mechanism involving the stop codon. For this reason, we designed a computer program using the yeast database genomic regions, and seeking two adjacent open reading frames separated only by a unique stop codon (called SORFs). Among the 58 SORFs identi®ed, eight displayed a stop codon bypass level ranging from 3 to 25%. For each of the eight sequences, we demonstrated the presence of a poly(A) mRNA. Using isogenic [PSI+] and [psi±] yeast strains, we showed that for two of the sequences the mechanism used is a bona ®de read-through. However, the six remaining sequences were not sensitive to the PSI state, indicating either a translation termination process independent of eRF3 or a new stop codon bypass mechanism. Our results demonstrate that the presence of a stop codon in a large ORF may not always correspond to a sequencing error, or a pseudogene, but can be a recoding signal in a functional gene. This empha-sizes that genome annotation should take into account the fact that recoding signals could be more frequently used than previously expected