Epigenetic control of polyamines by the prion [PSI+]

Prion proteins are found in mammals and yeast, and can transmit diseases and encode heritable phenotypic traits(1). In Saccharomyces cerevisiae, eRF3, Rnq1, Ure2 and Swi1 are functional proteins with a soluble conformation that can switch to a non-functional, amyloid conformation denoted as [PSI(+)], [PIN(+)], [URE3] and [SWI(+)], respectively(2,3). The prion [PSI+] corresponds to an aggregated conformation of the translational release factor eRF3, which suppresses nonsense codons(2). [PSI(+)] modifies cellular fitness and induces several phenotypes according to the genetic background(4,5). An elegant series of studies has demonstrated that several [PSI(+)]-induced phenotypes occur as a consequence of decreased translational termination efficiency(6,7). However, the genes whose expression levels are controlled by [PSI(+)] remain largely unknown. Here, we show that [PSI(+)] enhances expression of antizyme, a negative regulator of cellular polyamines, by modulating the +1 frameshifting required for its expression(8). Our study also demonstrates that [PSI(+)] greatly affects cellular polyamines in yeast. We show that modification of the cellular content of polyamines by the prion accounts for half of the [PSI(+)]-induced phenotypes. Antizyme is the first protein to be described for which expression of its functional form is stimulated by [PSI(+)].