The [URE3] prion is an aggregated form of Ure2p that can be cured by overexpression of Ure2p fragments

The [URE3] nonchromosomal genetic element is a prion of Ure2p, a regulator of nitrogen catabolism in Saccharomyces cerevisiae. Ure2p(1–65) is the prion domain of Ure2p, sufficient to propagate [URE3] in vivo. We show that full length Ure2p–green fluorescent protein (GFP) or a Ure2p(1–65)-GFP fusion protein is aggregated in cells carrying [URE3] but is evenly distributed in cells lacking the [URE3] prion. This indicates that [URE3] involves a self-propagating aggregation of Ure2p. Overexpression of Ure2p(1–65) induces the de novo appearance of [URE3] by 1,000-fold in a strain initially [ure-o], but cures [URE3] from a strain initially carrying the [URE3] prion. Overexpression of several other fragments of Ure2p or Ure2-GFP fusion proteins also efficiently cures the prion. We suggest that incorporation of fragments or fusion proteins into a putative [URE3] “crystal” of Ure2p poisons its propagation.

[URE3]非染色体遗传因子是酿酒酵母（Saccharomyces cerevisiae）中氮分解代谢调节因子Ure2p的朊病毒。Ure2p(1–65)为Ure2p的朊病毒结构域，足以在体内传播[URE3]。本研究证实，全长Ure2p-绿色荧光蛋白（GFP）或Ure2p(1–65)-GFP融合蛋白在携带[URE3]的细胞中会发生聚集，而在不含[URE3]朊病毒的细胞中则呈均匀分布状态，这表明[URE3]的形成涉及Ure2p的自我传播性聚集。对Ure2p(1–65)进行过表达，可使初始为[ure-o]的菌株中新出现[URE3]的频率提升1000倍，同时可从初始携带[URE3]朊病毒的菌株中清除[URE3]。对其他数种Ure2p片段或Ure2-GFP融合蛋白进行过表达，同样能够有效清除该朊病毒。我们推测，将此类片段或融合蛋白掺入Ure2p假想的[URE3]“晶体”结构中，会阻断其传播过程。