Prion formation [PSI+] and benefits in S. cerevisiae

Abstract

Prion formation in S. cerevisiae is still a relatively new field of yeast molecular biology. In opposition to prions in humans, these protein misfoldings are thought to be beneficial to cell survival in response to environmental stress. The prion state from Sup35 misfolding – a protein for translation termination – has been implicated in rescuing splicing efficiency and altering splicing factor abundance. To test whether the prion state, [PSI+], affects RNA splicing in either its intermediate or strong phenotype, “double mutants” of [PSI+] and a splicing factor deletion will be created through knock out PCR to observe possible positive genetic interactions. In deleting Snu66 from the genome of a [PSI+] intermediate strain, a positive genetic interaction was observed through a qualitative growth assay, indicating a positive genetic interaction between the Snu66 splicing factor and the intermediate phenotype of [PSI+]. The rescue of splicing efficiency by strong [PSI+] was confirmed through RT-qPCR to previous data. Together, the results show that PSI+ formation impacts RNA splicing, suggesting a direct relation between Sup35 function and splicing. The possible mechanisms for the effect of [PSI+] on translation termination include nonsense suppression and non-stop decay, altering function of splicing factors through additional domains, or decreased protein levels.