Prions affect the appearance of other prions:: The story of [PIN+]

Prions are self-propagating protein conformations. Recent research brought insight into prion propagation, but how they first appear is unknown. We previously established that the yeast non-Mendelian trait [PIN+] is required for the de novo appearance of the [PSI+] prion. Here, we show that the presence of prions formed by Rnq1 or Ure2 is sufficient to make cells [PIN+]. Thus, [PIN+] can be caused by more than one prion. Furthermore, an unbiased functional screen for [PIN+] prions uncovered the known prion gene, URE2, the proposed prion gene, NEW1, and nine novel candidate prion genes all carrying prion domains. Importantly, the de novo appearance of Rnq1::GFP prion aggregates also requires the presence of other prions, suggesting the existence of a general mechanism by which the appearance of prions is enhanced by heterologous prion aggregates.