Genome-wide translational changes induced by the prion [PSI+]

Prions are infectious proteins that can adopt a structural conformation different from that of the normal protein. This change of conformation is then propagated among other molecules of the same protein. Prions are associated with neurodegenerative diseases in mammals, but are also found in fungi (in the yeast Saccharomyces cerevisiae and the filamentous fungus Podospora anserina), in which they control heritable traits. They are widespread in wild yeast strains, suggesting a biologically important role. [PSI+] is one of the most widely studied yeast prions. It corresponds to an aggregated conformation of the translational release factor, eRF3, which suppresses nonsense codons. [PSI+] modifies cellular fitness, inducing various phenotypes, depending on the genetic background. However, the genes displaying [PSI+]-controlled expression remain largely unknown. We used the recently described ribosome profiling approach to identify genes displaying changes in expression in the presence of [PSI+]. This made it possible to determine the positions of all active ribosomes within the genome, in both [PSI+] and [PSI-] isogenic strains. Comparisons of the translatomes and transcriptomes of the two strains revealed that the primary effect of [PSI+] was to repress genes involved in the stress response. Thus, we provide the first description of the global translational effect of [PSI+] and a new genetic explanation of the phenotypic differences between [PSI-] and [PSI+] strains under stress conditions. Overall design: Comparisons of the translatomes and transcriptomes of the two strains. Comparisons of the translatomes of the two strains : a [PSI+] strain (two replicates) and a [PSI+] overexpressing SUP35-Cter strain.

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Baudin-Baillieu A, Legendre R, Kuchly C, Hatin I, Demais S, Mestdagh C, Gautheret D, Namy O