Prions of yeast as epigenetic phenomena: high protein "copy number" inducing protein "silencing".
Yeast infectious protein (prion) forms of the Ure2 and Sup35 proteins determine the nonchromosomal genes [URE3] and [PSI], and these are, therefore, the basis for a kind of epigenetic phenomena. In many systems, introduction of multiple copies of a DNA gene, or dsRNA copies of its sequence, results in the epigenetic silencing of that gene. In parallel with these homology effects, which act at the level of DNA or RNA, elevated copy number of the Ure2 and Sup35 proteins increases the frequency of their own "silencing" by prion formation. Both [URE3] and [PSI] appear to be due to self-propagating-amyloid formation of Ure2p and Sup35p, respectively. Another prion, [Het-s] of the filamentous fungus, Podospora anserina, is necessary for a normal cellular function, heterokaryon incompatibility. Since these prions are nonchromosomal genes, they are proteins acting as genes, a parallel to the fact that nucleic acids can catalyze enzymatic reactions.
Wickner
Reed B
RB
Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Edskes
Herman K
HK
Roberts
B Tibor
BT
Pierce
Michael
M
Baxa
Ulrich
U
D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D020868:Gene Silencing; D005800:Genes, Fungal; D005979:Glutathione Peroxidase; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D000682:Amyloid; D018832:Molecular Chaperones; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D018631:ras Proteins; D009584:Nitrogen