Yeast prions are “infectious.”

<p>A) A sexual cross of [<i>PRION</i>⁺] and [<i>prion⁻</i>] cells of opposite mating types results in a [<i>PRION</i>⁺] diploid, which can give rise to fourspores that are all [<i>PRION</i>⁺] after sporulation. Note: in the case of weak [<i>PSI</i>⁺] and [URE3], [<i>PRION</i>⁺]×[<i>prion</i>⁻] crosses do not always give a 4∶0 segregation in progeny. Some other random, non-Mendelian segregation ratios of progeny can be seen, such as 1∶4, 1∶3, 3∶1, 4∶0, as well as 2∶2, due to their meiotic instabilities. B) Mating a [<i>PRION</i>⁺] donor with a [<i>prion</i>⁻] recipient carrying a <i>kar1</i> mutation (which prevents nuclear fusion of the mating partners) will result in formation of a pseudodiploid carrying a mixed cytoplasm of the two mating partners. The pseudodiploid will give rise to haploid cytoductants containing either the donor or recipient nucleus. Shown is a cytoductant containing the recipient nucleus with a <i>kar1</i> mutation. C) Transformation of [<i>prion</i>⁻] spheroplasts (yeast with cell wall removed) with amyloid fibers assembled from recombinant prion protein can result in <i>de novo</i> formation of heritable [<i>PRION</i>⁺] in the transformed cells. A <i>URA3</i> plasmid (green circle) was used as a selection marker for the transformation. Solid red color indicates the soluble, diffused prion-determinant protein, whereas red dots indicate the prion protein is in an aggregated prion conformation.</p

Environmental regulation of yeast prions.

<p>Prionogenesis is a multistep process in which the prion determinant protein undergoes changes in its secondary structure to form intermediate species and then prion (amyloid) fibrils; this process relies on other cellular machinery to drive these changes. Thermal stress results in the relocalization of heat-shock factor 1 (Hsf1) from the cytoplasm to the nucleus; here it binds to the heat-shockelement (HSEs) of heat-shock–protein genes, activating their transcription. Consequentially, a diverse group of heat-shock proteins (HSPs) are synthesized. Many HSPs (molecular chaperones) play important roles in prion formation and propagation, including Hsp104, Hsp70-Ssa, and Hsp40-Sis1. In a similar manner, general stresses including oxidative, osmotic, and heat stresses, activate a separate pathway in which Msn2,4 binds to the stress-response element (STREs) of stress-response genes, thereby activating their transcription. Some HSP genes also contain one or more STREs at their 5′-regulatory regions. Deletion of the <i>MSN2</i> gene results in a drastic increase of the frequency of [<i>PSI</i>⁺] formation, suggesting that some stress-response proteins are also involved in prion formation. However, the identity of the Msn2,4 targets that are involved in prionogenesis remain elusive. Note: for simplicity, only the two major stress-response pathways that are regulated by Hsf1 and Msn2,4 are shown.</p