title: A yeast prion, Mod5, promotes acquired drug resistance and cell survival under environmental stress.
abstract: Prion conversion from a soluble protein to an aggregated state may be involved in the cellular adaptation of yeast to the environment. However, it remains unclear whether and how cells actively use prion conversion to acquire a fitness advantage in response to environmental stress. We identified Mod5, a yeast transfer RNA isopentenyltransferase lacking glutamine/asparagine-rich domains, as a yeast prion protein and found that its prion conversion in yeast regulated the sterol biosynthetic pathway for acquired cellular resistance against antifungal agents. Furthermore, selective pressure by antifungal drugs on yeast facilitated the de novo appearance of Mod5 prion states for cell survival. Thus, phenotypic changes caused by active prion conversion under environmental selection may contribute to cellular adaptation in living organisms.
authors.affiliation: Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Genjiro
authors.initials: G
authors.lastname: Suzuki
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Shimazu
authors.forename: Motomasa
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000935:Antifungal Agents / Q000494:pharmacology*; D053898:Biosynthetic Pathways; D003433:Crosses, Genetic; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000096:biosynthesis; D005472:Fluorouracil / Q000494:pharmacology; D050296:Microbial Viability; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012331:RNA, Fungal / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012641:Selection, Genetic; D012995:Solubility; D013312:Stress, Physiological
chemical_list: D000935:Antifungal Agents; D011328:Prions; D012331:RNA, Fungal; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer; D019883:Alkyl and Aryl Transferases; C068392:MOD5 protein, S cerevisiae; D005472:Fluorouracil; D004875:Ergosterol