Abstract
Although transcription factors are prevalent among yeast prion proteins, the role of prion-mediated transcriptional regulation remains elusive. Here, we show that the yeast prion [SWI+] abolishes flocculin (FLO) gene expression and results in a complete loss of multicellularity. Further investigation demonstrates that besides Swi1, multiple other proteins essential for FLO expression, including Mss11, Sap30, and Msn1 also undergo conformational changes and become inactivated in [SWI+] cells. Moreover, the asparagine-rich region of Mss11 can exist as prion-like aggregates specifically in [SWI+] cells, which are SDS resistant, heritable, and curable, but become metastable after separation from [SWI+]. Our findings thus reveal a prion-mediated mechanism through which multiple regulators in a biological pathway can be inactivated. In combination with the partial loss-of-function phenotypes of [SWI+] cells on non-glucose sugar utilization, our data therefore demonstrate that a prion can influence distinct traits differently through multi-level regulations, providing insights into the biological roles of prions.
Original language | English (US) |
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Pages (from-to) | 2865-2878 |
Number of pages | 14 |
Journal | Cell reports |
Volume | 13 |
Issue number | 12 |
DOIs | |
State | Published - Dec 29 2015 |
Funding
The authors thank Dr. G. Braus (Georg August University Göttingen, Institute for Microbiology and Genetics) for the gift of strains and plasmids as well as S. Valtierra and D. Goncharoff for critical comments and manuscript editing. This work was supported by grants from the NIH (R01NS056086 and R01GM10045) and National Science Foundation (MCB 1122135) to L.L. and the China Scholarship Council (file no. [2012]3022-201208110572) and National Natural Science Foundation of China (81100809 and 81271417) to Y.Z.
Keywords
- SWI/SNF
- Saccharomyces cerevisiae
- Swi1
- amyloids
- filamentous growth
- flocculin
- multicellularity
- prion
- protein conformation change
- protein-aggregation
- yeast
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology