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Fungal prions

Fungal prions have been investigated, leading to a deeper understanding of disease-forming mammalian prions.

Prion-like proteins are found naturally in some plants and non-mammalian animals. Some of these are not associated with any disease state and may possibly even have a useful role[1]. Because of this, scientists reasoned that such proteins could give some sort of evolutionary advantage to their host. This was suggested to be the case in a species of fungus, Podospora anserina. Genetically compatible colonies of this fungus can merge together and share cellular contents such as nutrients and cytoplasm. A natural system of protective "incompatibility" proteins exists to prevent promiscuous sharing between unrelated colonies. One such protein, called HET-S, adopts a prion-like form in order to function properly [2]. The prion form of HET-S spreads rapidly throughout the cellular network of a colony and can convert the non-prion form of the protein to a prion state after compatible colonies have merged [3]. However, when an incompatible colony tries to merge with a prion-containing colony, the prion causes the "invader" cells to die, ensuring that only related colonies obtain the benefit of sharing resources.


Sup35p & Ure2p

In 1965, Brian Cox, a geneticist working with the yeast Saccharomyces cerevisiae, described a genetic trait (termed PSI+) with an unusual pattern of inheritance. The initial discovery of PSI+ was made in a strain auxotrophic for the adenine due to a nonsense mutation [1] Despite many years of effort, Cox could not identify a conventional mutation that was responsible for the PSI+ trait.

In 1994, yeast geneticist Reed Wickner correctly hypothesized that PSI+ as well as another mysterious heritable trait, URE3, resulted from prion forms of certain normal cellular proteins [4]. It was soon noticed that heat shock proteins (which help other proteins fold properly) were intimately tied to the inheritance and transmission of PSI+ and many other yeast prions. Since then, researchers have unravelled how the proteins that code for PSI+ and URE3 can convert between prion and non-prion forms, as well as the consequences of having intracellular prions. When exposed to certain adverse conditions, PSI+ cells actually fare better than their prion-free siblings [5]; this finding suggests that, in some proteins, the ability to adopt a prion form may result from positive evolutionary selection [6]. It has been speculated that the ability to convert between prion infected and prion-free forms enables yeast to quickly and reversibly adapt in variable environments. Nevertheless, Wickner maintains that URE3 and PSI+ are diseases [7].

Further investigation found that PSI+ is the misfolded form of Sup35, which is an important factor for translation termination during protein synthesis [2]. It is believed that [PSI+] causes suppression of nonsense mutations by sequestering functional Sup35 in non-functional aggregates, thereby allowing stop codon readthrough. [PIN+], in turn, is the misfolded form of the protein Rnq1. However, the normal function of this protein is unknown to date. It is of note that for the induction of most variants of [PSI+], the presence of [PIN+] is required. Though reasons for this are poorly understood, it is suggested that [PIN+] aggregates may act as “seeds” for the polymerization of [PSI+] [3].

Two modified versions of Sup35 have been created that can induce PSI+ in the absence of [PIN+] when overexpressed. One version was created by digestion of the gene with BalI, which results in a protein consisting of only the M and N portions of Sup35 [4]. The other is a fusion of Sup35NM with HPR, a human membrane receptor protein.

Laboratories commonly identify [PSI+] by growth of a strain auxotrophic for adenine on media lacking adenine, similar to that used by Cox et al. These strains cannot synthesize adenine due to a nonsense mutation in one of the enzymes involved in biosynthetic pathway. When the strain is grown on yeast-extract/dextrose/peptone media (YPD), the blocked pathway results in buildup of a red-colored intermediate compound, which is exported from the cell due to its toxicity. Hence, color is an alternative method of identifying [PSI+] -- [PSI+] strains are white or pinkish in color, and [psi-] strains are red. A third method of identifying [PSI+] is by the presence of Sup35 in the pelleted fraction of cellular lysate.


Fungal Prions
Protein Natural Host Normal Function Prion State Prion Phenotype
Ure2p Saccharomyces cerevisiae Nitrogen catabolite repressor [URE3] Growth on poor nitrogen sources
Sup35p Saccharomyces cerevisiae Translation termination factor [PSI+] Increased levels of nonsense suppression
Rnq1p Saccharomyces cerevisiae Protein template factor [RNQ+] Promotes aggregation of other prions
HET-S Podospora anserina Regulates heterokaryon incompatibillity [Het-s] Heterokaryon formation between incompatible strains

As of 2003, the following proteins in Saccharomyces cerevisiae had been identified or postulated as prions:

  • Sup35p, forming the [PSI+] element;
  • Ure2p, forming the [URE3] element;
  • Rnq1p, forming the [RNQ+] element (also known as [PIN+])
  • A fifth prion protein, forming the [ISP+] element remains to be identified.


  1. ^ A census of glutamine/asparagine-rich regions: Implications for their conserved function and the prediction of novel prions. PNAS USA. 2000 Oct 24; 97(22): 11910-5 Free text
  2. ^ The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog. PNAS USA. 1997 Sep 2; 94(18): 9773-8 Free text
  3. ^ Amyloid aggregates of the HET-S prionprotein are infectious. PNAS USA. 2002 May 28; 99(11): 7402-7 Free text
  4. ^ [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994 Apr 22; 264(5158): 566-9 Abstract
  5. ^ A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature. 2000 Sep 28; 407(6803): 477-83 Abstract
  6. ^ A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution. J Mol Biol. 2002 Feb 22; 316(3): 409-19 Abstract
  7. ^ Yeast prions [URE3] and [PSI+] are diseases. PNAS USA. 2005 July 26; 102(30): 10575-80 Free text

See also

  • Prion
  • Sup35p
  • Epigenetics
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Fungal_prions". A list of authors is available in Wikipedia.
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