Genome-wide Translational Changes Induced by the Prion [PSI+]

Summary Prions are infectious proteins that can adopt a structural conformation that is then propagated among other molecules of the same protein. [ PSI + ] is an aggregated conformation of the translational release factor eRF3. [ PSI + ] modifies cellular fitness, inducing various phenotypes depending on genetic background. However, the genes displaying [ PSI + ]-controlled expression remain unknown. We used ribosome profiling in isogenic [ PSI + ] and [ psi − ] strains to identify the changes induced by [ PSI + ]. We found 100 genes with stop codon readthrough events and showed that many stress-response genes were repressed in the presence of [ PSI + ]. Surprisingly, [ PSI + ] was also found to affect reading frame selection independently of its effect on translation termination efficiency. These results indicate that [ PSI + ] has a broader impact than initially anticipated, providing explanations for the phenotypic differences between [ psi − ] and [ PSI + ] strains.