The stability of ribosomal DNA (rDNA) is maintained through transcriptional silencing by the NAD-dependent histone deacetylase Sir2 in . Alongside proteostasis, rDNA stability is a crucial factor regulating the replicative lifespan of . The unfolded protein response (UPR) is induced by misfolding of proteins or an imbalance of membrane lipid composition and is responsible for degrading misfolded proteins and restoring endoplasmic reticulum (ER) membrane homeostasis. Recent investigations have suggested that the UPR can extend the replicative lifespan of yeast by enhancing protein quality control mechanisms, but the relationship between the UPR and rDNA stability remains unknown. In this study, we found that the deletion of , which encodes an ER protein of unknown molecular function, activates the UPR by inducing lipid bilayer stress. In Δ cells, the UPR and the cell wall integrity pathway are activated independently of each other, and the high osmolarity glycerol (HOG) pathway is activated in a manner dependent on Ire1, which mediates the UPR. Activated Hog1 translocates the stress response transcription factor Msn2 to the nucleus, where it promotes the expression of nicotinamidase Pnc1, a well-known Sir2 activator. Following Sir2 activation, rDNA silencing and rDNA stability are promoted. Furthermore, the loss of other ER proteins, such as Pmt1 or Bst1, and ER stress induced by tunicamycin or inositol depletion also enhance rDNA stability in a Hog1-dependent manner. Collectively, these findings suggest that the induction of the UPR enhances rDNA stability in by promoting the Msn2-Pnc1-Sir2 pathway in a Hog1-dependent manner.

中文翻译：

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ARV1 缺陷通过激活酿酒酵母中的未折叠蛋白反应诱导脂质双层应激并增强 rDNA 稳定性


核糖体 DNA (rDNA) 的稳定性是通过 NAD 依赖性组蛋白脱乙酰酶 Sir2 的转录沉默来维持的。除了蛋白质稳态外，rDNA 稳定性也是调节复制寿命的关键因素。未折叠蛋白反应（UPR）是由蛋白质错误折叠或膜脂组成失衡诱导的，负责降解错误折叠蛋白质并恢复内质网（ER）膜稳态。最近的研究表明，UPR 可以通过增强蛋白质质量控​​制机制来延长酵母的复制寿命，但 UPR 与 rDNA 稳定性之间的关系仍不清楚。在这项研究中，我们发现编码未知分子功能的ER蛋白的缺失通过诱导脂质双层应激来激活UPR。在Δ细胞中，UPR和细胞壁完整性途径彼此独立地被激活，并且高渗透甘油（HOG）途径以依赖于介导UPR的Ire1的方式被激活。激活的 Hog1 将应激反应转录因子 Msn2 转移到细胞核，促进烟酰胺酶 Pnc1（一种著名的 Sir2 激活剂）的表达。 Sir2 激活后，rDNA 沉默和 rDNA 稳定性得到促进。此外，其他 ER 蛋白（例如 Pmt1 或 Bst1）的丢失以及衣霉素或肌醇消耗诱导的 ER 应激也以 Hog1 依赖性方式增强 rDNA 稳定性。总的来说，这些发现表明 UPR 的诱导通过以 Hog1 依赖性方式促进 Msn2-Pnc1-Sir2 途径来增强 rDNA 稳定性。