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

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.