Heritable Remodeling of Yeast Multicellularity by an Environmentally Responsive Prion

Abstract

SUMMARY Prion proteins undergo self-sustaining conforma-tional conversions that heritably alter their activities. Many of these proteins operate at pivotal positions in determining how genotype is translated into pheno-type. But the breadth of prion influences on biology and their evolutionary significance are just beginning to be explored. We report that a prion formed by the Mot3 transcription factor, [MOT3+], governs the acquisition of facultative multicellularity in the budding yeast Saccharomyces cerevisiae. The traits governed by [MOT3+] involved both gains and losses of Mot3 regulatory activity. [MOT3+]-dependent expression of FLO11, a major determinant of cell-cell adhesion, produced diverse lineage-specific multicellular phenotypes in response to nutrient deprivation. The prions themselves were induced by ethanol and eliminated by hypoxia—conditions that occur sequentially in the natural respiro-fermen-tative cycles of yeast populations. These data demonstrate that prions can act as environmentally responsive molecular determinants of multicellularity and contribute to the natural morphological diversity of budding yeast.

Heterochromatin aggregation during DNA elimination in Tetrahymena is facilitated by a prion-like protein

“…It seems the detected Jub6p multimers migrate faster than the previously reported amyloid aggregates (Alberti et al, 2009;Halfmann et al, 2012;Holmes et al, 2013). This suggests that Jub6p aggregates are stable only as oligomers.…”

“…Prion-like proteins play important pathological roles in the development of neurodegenerative diseases (Jucker and Walker, 2013), in addition to physiological roles in various biological processes, such as transcriptional regulation for environmental adaptability, translational regulation in the formation of long-term memory and RNA localization in cell cycle regulation (Halfmann et al, 2012;Holmes et al, 2013;Lee et al, 2013;Majumdar et al, 2012;Si et al, 2003). Because heterochromatin bodies are considered nucleoprotein aggregates, we chose to investigate the involvement of a prion-like protein in this process in Tetrahymena.…”

Prions, amyloids, and RNA: Pieces of a puzzle

“…43 Notably, a specific mechanism of induction and elimination driven by changes in environmental conditions has been described for this prion: increasing ethanol concentration promotes [MOT3 C ] formation, while hypoxia eliminates it by repressing the expression of the MOT3 gene. 85 Such changes in environmental conditions do occur during fermentation, and, taking into consideration that the appearance of [MOT3 C ] causes FLO11-mediated flocculation, which is important for survival, this prion is apparently beneficial, although, in fact, this has not been confirmed outside of the laboratory. 85 [URE3] does not provide any apparent advantages to yeast, and some strains or conformational variants of this prion significantly inhibit vegetative growth.…”

“…85 Such changes in environmental conditions do occur during fermentation, and, taking into consideration that the appearance of [MOT3 C ] causes FLO11-mediated flocculation, which is important for survival, this prion is apparently beneficial, although, in fact, this has not been confirmed outside of the laboratory. 85 [URE3] does not provide any apparent advantages to yeast, and some strains or conformational variants of this prion significantly inhibit vegetative growth. 88 Also, [SWI C ] manifests not only beneficial, but also harmful phenotypes: it inhibits vegetative growth on media containing non-fermentable carbon sources.…”

Heterogeneous seeding of HET-s(218–289) and the mutability of prion structures

“…17 HET-s(218-289) is a useful model prion for studying the biophysical interactions of different types of amyloids. Unlike the prions of S. cerevisiae, 18,19 HET-s(218-289) is not Q/N rich, making its amino acid composition similar to those of most other pathological amyloids. While HET-s(218-289) is smaller than the putative prion-forming domain (the proteinase K-resistant core) of PrP, 20 it is large enough to form a complex amyloid structure that is fundamentally irreproducible in short peptide systems.…”