Interaction of Prions Causes Heritable Traits in Saccharomyces cerevisiae

• DOI: 10.1371/journal.pgen.1006504
• Publication Date: 2017-01-09T19:59:27Z
• Authors: Anton A. Nizhnikov; Tatyana A. Ryzhova; Kirill V. Volkov; Sergey P. Zadorsky; Julia V. Sopova; Sergey G. Inge-Ve...; Alexey P. Galkin
• Keywords: Proteomics; 0301 basic medicine; 0303 health sciences; Saccharomyces cerevisiae Proteins; Chromosomal Proteins, Non-Histone; Prions; Galactose; Saccharomyces cerevisiae; QH426-470; DNA-Binding Proteins; Meiosis; 03 medical and health sciences; Microscopy, Fluorescence; Codon, Nonsense; Genetics; Research Article; Peptide Termination Factors; Plasmids; Sequence Deletion; Transcription Factors

The concept of "protein-based inheritance" defines prions as epigenetic determinants that cause several heritable traits in eukaryotic microorganisms, such as Saccharomyces cerevisiae and Podospora anserina. Previously, we discovered a non-chromosomal factor, [NSI+], which possesses the main features of yeast prions, including cytoplasmic infectivity, reversible curability, dominance, and non-Mendelian inheritance in meiosis. This factor causes omnipotent suppression of nonsense mutations in strains of S. cerevisiae bearing a deleted or modified Sup35 N-terminal domain. In this work, we identified protein determinants of [NSI+] using an original method of proteomic screening for prions. The suppression of nonsense mutations in [NSI+] strains is determined by the interaction between [SWI+] and [PIN+] prions. Using genetic and biochemical methods, we showed that [SWI+] is the key determinant of this nonsense suppression, whereas [PIN+] does not cause nonsense suppression by itself but strongly enhances the effect of [SWI+]. We demonstrated that interaction of [SWI+] and [PIN+] causes inactivation of SUP45 gene that leads to nonsense suppression. Our data show that prion interactions may cause heritable traits in Saccharomyces cerevisiae.