Prions of yeast fail to elicit a transcriptional response

Amyloid deposits are associated with numerous human diseases. The [URE3] prion of Saccharomyces is an infectious, inactive, amyloid form of the Ure2p protein. Despite the presence of large prion aggregates in [URE3] yeast, the only apparent phenotypes associated with the prion are attributable to loss of Ure2p function. We used cDNA microarrays to look for genes in yeast that are differentially expressed in the presence of the [URE3] prion and which might act to mitigate the detrimental effects of the prion aggregates. On comparing [URE3] vs. ure2 yeast, we were surprised to find that the only expression changes detected were attributable to the low level of residual Ure2p activity in the [URE3] cells. Interestingly, in addition to repressing the activity of genes required for utilization of poor nitrogen sources when yeast are grown in the presence of a good nitrogen source, Ure2p appears to be involved in stimulating some of these same genes in the absence of a good nitrogen source.