Prions represent epigenetic regulator proteins that can self-propagate their structure and confer their misfolded structure and function on normally folded proteins. Like the mammalian prion PrPSc, prions also occur in fungi. While a few prions, like Swi1, affect gene expression, none are shown to affect heterochromatin structure and function. In fission yeast and metazoans, histone methyltransferase Clr4/Suv39 causes H3-Lys9 methylation, which is bound by the chromodomain protein Swi6/HP1 to assemble heterochromatin. Earlier, we showed that sng2-1 mutation in the Cut4 subunit of anaphase-promoting complex abrogates heterochromatin structure due to defective binding and recruitment of Swi6. Here, we demonstrate that the Cut4p forms a non-canonical prion form, designated as [SNG2], which abrogates heterochromatin silencing. [SNG2] exhibits various prion-like properties, e.g. non-Mendelian inheritance, requirement of Hsp proteins for its propagation, de novo generation upon cut4 overexpression, reversible curing by guanidine, cytoplasmic inheritance and formation of infectious protein aggregates, which are dissolved upon overexpression of hsp genes. Interestingly, [SNG2] prion imparts an enhanced tolerance to stress conditions, supporting its role in promoting cell survival under environmental stress during evolution.

中文翻译：

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[SNG2] 是 Cut4/Apc1 的朊病毒形式，赋予裂变酵母中异染色质沉默缺陷的非孟德尔遗传


朊病毒代表表观遗传调节蛋白，可以自我繁殖其结构并将其错误折叠的结构和功能赋予正常折叠的蛋白质。与哺乳动物朊病毒 PrPSc 一样，朊病毒也存在于真菌中。虽然一些朊病毒（如 Swi1）会影响基因表达，但没有一个朊病毒会影响异染色质的结构和功能。在裂变酵母和后生动物中，组蛋白甲基转移酶 Clr4/Suv39 引起 H3-Lys9 甲基化，H3-Lys9 甲基化与染色质结构域蛋白 Swi6/HP1 结合以组装异染色质。早些时候，我们表明，由于 Swi6 的结合和募集缺陷，后期促进复合物 Cut4 亚基中的 sng2-1 突变消除了异染色质结构。在这里，我们证明 Cut4p 形成一种非经典朊病毒形式，命名为 [SNG2]，它消除了异染色质沉默。[SNG2] 表现出各种朊病毒样特性，例如非孟德尔遗传、需要 Hsp 蛋白进行繁殖、cut4 过表达时的从头生成、胍的可逆固化、细胞质遗传和感染性蛋白质聚集体的形成，这些聚集体在 HSP 基因过表达时溶解。有趣的是，[SNG2] 朊病毒赋予了对压力条件的更强耐受性，支持其在进化过程中促进细胞在环境压力下存活的作用。