Nucleic Acids Research, 2003, Vol. 31, No. 9 2289-2296
© 2003 Oxford University Press
Identification of stop codon readthrough genes in Saccharomyces cerevisiae
Laboratoire de Génétique Moléculaire de la Traduction, 1 Laboratoire de Bioinformatique des Génomes, Institut de Génétique et Microbiologie, Université Paris-Sud, 91405 Orsay Cedex, France and 2 Laboratoire de Génétique Moléculaire, Ecole Normale Superieure 46, rue dUlm, 75230 Paris cedex 05, France
*To whom correspondence should be addressed at present address: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. Tel: +44 1223 336918; Fax: +44 1223 336926; Email: on205{at}mole.bio.cam.ac.uk
We specifically sought genes within the yeast genome controlled by a non-conventional translation 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 identified, 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 fide readthrough. 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 emphasizes that genome annotation should take into account the fact that recoding signals could be more frequently used than previously expected.
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