Podbelskogo sh., 3, Pushkin, 196608 St. Petersburg, Russia.
St. Petersburg State University, Universitetskaya nab., 7/9, 199034 St. Petersburg, Russia.
Genes (Basel). 2019 Mar 12;10(3):212. doi: 10.3390/genes10030212.
Prions are infectious, self-perpetuating protein conformers. In mammals, pathological aggregation of the prion protein causes incurable neurodegenerative disorders, while in yeast , prion formation may be neutral or even beneficial. According to the prevailing contemporary point of view, prion formation is considered to be a functional inactivation of the corresponding protein whose conformational state shifts from the functional monomeric one to the infectious aggregated one. The Swi1 protein forms the [⁺] prion and belongs to the nucleosome remodeler complex SWI/SNF controlling the expression of a significant part of the yeast genome. In this work, we performed RNA sequencing of isogenic strains grown on the media containing galactose as the sole carbon source. These strains bore the [⁺] prion or had its structural gene deleted. The comparative analysis showed that [⁺] affects genome expression significantly weaker as compared to the deletion. Moreover, in contrast to [⁺], the deletion causes the general inhibition of translation-related genes expression and chromosome I disomy. At the same time, the [⁺] prion exhibits a specific pattern of modulation of the metabolic pathways and some biological processes and functions, as well as the expression of several genes. Thus, the [⁺] prion only partially corresponds to the loss-of-function of and demonstrates several gain-of-function traits.
朊病毒是具有感染性的、自我维持的蛋白质构象。在哺乳动物中，朊病毒蛋白的病理性聚集导致不可治愈的神经退行性疾病，而在酵母中，朊病毒的形成可能是中性的，甚至是有益的。根据当前流行的观点，朊病毒的形成被认为是相应蛋白的一种功能失活，其构象状态从功能性单体转变为感染性聚集体。Swi1 蛋白形成[⁺]朊病毒，属于核小体重塑复合物 SWI/SNF，该复合物控制着酵母基因组中很大一部分的表达。在这项工作中，我们对在含有半乳糖作为唯一碳源的培养基中生长的同基因菌株进行了 RNA 测序。这些菌株携带[⁺]朊病毒或其结构基因被删除。比较分析表明，与缺失相比，[⁺]对基因组表达的影响要弱得多。此外，与[⁺]不同，缺失会导致与翻译相关的基因表达和染色体 I 二倍体的普遍抑制。同时，[⁺]朊病毒表现出对代谢途径和一些生物学过程和功能以及几个基因表达的特定调节模式。因此，[⁺]朊病毒仅部分对应于的功能丧失，并表现出几种功能获得的特征。
