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Published on: March 7, 2019
The Yeast Prion [SWI(+)] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators
Zhiqiang Du1, Ying Zhang2, Liming Li1
1Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Searle 7-650, Chicago, IL 60611, USA.
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.
Insights
The yeast prion [SWI(+)] inactivates multiple proteins, halting flocculin gene expression and multicellularity. This reveals a novel prion-mediated pathway affecting distinct traits through multi-level regulation.
Area of Science:
- Molecular Biology
- Yeast Genetics
- Prion Biology
Background:
- Transcription factors are common in yeast prion proteins, but their role in prion-mediated transcriptional regulation is unclear.
- Yeast prions are self-propagating protein conformers influencing cellular phenotypes.
Purpose of the Study:
- To investigate the role of the yeast prion [SWI(+)] in transcriptional regulation.
- To elucidate the mechanism by which [SWI(+)] affects gene expression and cellular traits.
Main Methods:
- Analysis of flocculin (FLO) gene expression in [SWI(+)] yeast.
- Investigation of protein conformational changes and aggregation of Swi1, Mss11, Sap30, and Msn1.
- Characterization of Mss11 prion-like aggregates (SDS resistance, heritability, curability).
Main Results:
- The [SWI(+)] prion abolishes FLO gene expression, leading to complete loss of multicellularity.
- Key FLO expression regulators (Swi1, Mss11, Sap30, Msn1) are inactivated via conformational changes in [SWI(+)] cells.
- Mss11 forms prion-like, SDS-resistant aggregates in [SWI(+)] cells, impacting its function.
Conclusions:
- A prion-mediated mechanism inactivates multiple regulators within a biological pathway.
- [SWI(+)] influences distinct traits (multicellularity, sugar utilization) differently through multi-level regulation.
- This study provides insights into the diverse biological roles of prions in yeast.
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