A brief overview of the Swi1 prion-[SWI+]

Abstract

Prion and prion-like phenomena are involved in the pathology of numerous human neurodegenerative diseases. The budding yeast, Saccharomyces cerevisiae, has a number of endogenous yeast prions-epigenetic elements that are transmitted as altered protein conformations and often manifested as heritable phenotypic traits. One such yeast prion, [SWI+], was discovered and characterized by our laboratory. The protein determinant of [SWI+], Swi1 was found to contain an amino-terminal, asparagine-rich prion domain. Normally, Swi1 functions as part of the SWI/SNF chromatin remodeling complex, thus, acting as a global transcriptional regulator. Consequently, prionization of Swi1 leads to a variety of phenotypes including poor growth on non-glucose carbon sources and abolishment of multicellular features-with implications on characterization of [SWI+] as being detrimental or beneficial to yeast. The study of [SWI+] has revealed important knowledge regarding the chaperone systems supporting prion propagation as well as prion-prion interactions with [PSI+] and [RNQ+]. Additionally, an intricate regulatory network involving [SWI+] and other prion elements governing multicellular features in yeast has begun to be revealed. In this review, we discuss the current understanding of [SWI+] in addition to some possibilities for future study.

Figure 1.

A schematic diagram showing Swi1 protein organization. (A) The Swi1 protein consists of three regions. The N region is highly enriched in asparagine (N) residues, holds the prion domain (PrD) and can form fibrils to seed [SWI⁺] formation (Du et al.2010). The middle Q region is rich in glutamine (Q) residues and modulates the aggregation pattern of the N region and Swi1 functions. The C-terminal located C region harbors the functional domain of Swi1. (B) The sequence of the N region is shown. The extreme N-terminal region, Swi1_1–38—shown to be able to stably transmit the prion confirmation in the absence of full-length Swi1—is underlined in black (Crow, Du and Li 2011). A reported amyloidogenic region, Swi1_239–259, whose role in prionogenesis has not been tested, is also underlined (in green) (Sant’Anna et al.2016). Asparagine and glutamine residues are highlighted in red and blue, respectively.

Figure 2.

Yeast cells harboring [SWI⁺] display a variety of phenotypes. Shown are major characterized phenotypes of the [SWI⁺] prion in yeast. Moving from left to right: by expression from a plasmid, fluorescently tagged Swi1 or a Swi1-PrD-containing fragment (e.g. NQ-YFP) aggregates in [SWI⁺] but is diffuse in [swi⁻] cells (Du et al. 2008, 2010). [SWI⁺]-containing cells exhibit poor growth on non-glucose carbon sources such as raffinose compared to [swi⁻] cells as shown (Du et al.2008). Multicellular features including flocculation, adhesive growth (observed via crystal blue staining after washing) and diploid pseudohyphae formation on SLAD (synthetic low ammonium dextrose) media are abolished in the presence of [SWI⁺] (Du, Zhang and Li 2015). [SWI⁺] cells are easily washed away in a wash assay and display enhanced mobility and an ability to migrate in flowing water in the illustrated raindrop assay (Newby and Lindquist 2017).

Figure 3.

Regulation of multicellular features by prion proteins in yeast. The yeast prion proteins of Swi1, Cyc8 and Mot3 are regulators of FLO gene expression. In the non-prion state, Swi1 (as a component of the SWI/SNF chromatin remodeling complex) promotes FLO gene expression; Mot3 and Cyc8 (subunit of the Cyc8-Tup1 co-repressor complex) act as transcriptional repressors of FLO genes (Barrales et al.; Holmes et al.2013). The [MOT3⁺] prion promotes multicellular features by enhancing FLO gene expression, whereas [SWI⁺] abolishes FLO gene expression and thus eliminates multicellular features (Holmes et al.; Du, Zhang and Li 2015). The Cyc8 prion ([OCT⁺]) would be predicted to remove a source of repression and, thus, increase FLO gene expression. Yeast can harbor multiple prions and the interaction among the three prions may intricately modulate FLO gene expression.