Nitrogen source and the retrograde signalling pathway affect detection, not generation, of the [URE3] prion

Abstract

[URE3] is an infectious (prion) inactive amyloid form of Ure2p, a regulator of nitrogen catabolism. [URE3] clones are selected on NH(4) (+), using their derepressed expression of DAL5 to allow uptake of ureidosuccinate (USA). We previously reported that mks1Delta prevents generation of [URE3] and others reported that glutamate in the medium or the elevated glutamate in mks1Delta strains blocks [URE3] generation. We show here that elevated glutamate does not block [URE3] generation, but that neither does mks1Delta. Rather, a post-transcriptional effect on DAL5 of mks1Delta through the retrograde regulation pathway prevents detection of [URE3] prion-containing colonies. Moreover, the presence of both ammonia and glutamate blocks USA uptake in a known [URE3] strain, so that detection of the prion is prevented, rather than its generation.