A new prion controls fungal cell fusion incompatibility.

In solving a genetic puzzle posed by George Rizet in 1952 (1), Coustou, Deleu, Saupe, and Begueret report (2) evidence for the first prion (infectious protein) that carries out a normal function. It was studies of scrapie that gave rise to the prion concept, namely, that a normal cellular protein could change to an abnormal form (the prion form) that may be unable to carry out its normal function, but has acquired the ability to convert its normal form into this same abnormal (prion) form. This altered protein, by catalyzing, not its own synthesis, but its own alteration, becomes an infectious agent (a prion) if it can get from cell to cell or from individual to individual (reviewed in refs. 3–6). Until now, all prions have seemed to cause diseases. Scrapie, Creutzfeldt–Jakob disease, Mad Cow disease, etc. in mammals are invariably lethal neurological diseases involving an altered form of PrP (prion protein), a nonessential cell surface protein (3–6). The non-Mendelian genetic element of Saccharomyces cerevisiae, [URE3] (for ureidosuccinate), is due to a prion change of Ure2p, a regulator of nitrogen metabolism, and results in slow-growing cells (7). [PSI], also a yeast prion, is due to an aggregating form of Sup35p, one of the translation termination proteins whose misfunction in cells carrying [PSI] results in abnormal read-through of translation termination codons (reviewed in ref. 7). This is clearly hazardous to one’s health, but [PSI] strains seem healthy if no suppressor tRNA is around to read the translation termination codon as an amino acid. The [Het-s] prion of the filamentous fungus Podospora anserina causes cell death, but it is a purposeful cell death designed to limit the spread of fungal viruses by preventing cytoplasmic exchange between two colonies.