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