title: The Yeast Prion [SWI(+)] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators Required for Flocculin Gene Expression.
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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Searle 7-650, Chicago, IL 60611, USA. Electronic address: z-du@northwestern.edu.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Du
authors.affiliation: College of Life Sciences and Bioengineering, Beijing Jiaotong University, No. 3 Shangyuan Residence, Haidian District, Beijing 100044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Searle 7-650, Chicago, IL 60611, USA. Electronic address: limingli@northwestern.edu.
authors.forename: Liming
authors.initials: L
authors.lastname: Li
mesh_terms: D015966:Gene Expression Regulation, Fungal; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
keywords: SWI/SNF; Saccharomyces cerevisiae; Swi1; amyloids; filamentous growth; flocculin; multicellularity; prion; protein conformation change; protein-aggregation; yeast