Nuclear RNA exosome is the main 3'→5' RNA degradation and processing complex in eukaryotic cells and its dysregulation therefore impacts gene expression and viability. In this work we show that RNA exosome activity is necessary for maintaining cell wall stability in yeast Saccharomyces cerevisiae. While the essential RNA exosome catalytic subunit Dis3 provides exoribonuclease catalytic activity, the second catalytic subunit Rrp6 has a non-catalytic role in this process. RNA exosome cofactors Rrp47 and Air1/2 are also involved. RNA exosome mutants undergo osmoremedial cell lysis at high temperature or at physiological temperature upon treatment with cell wall stressors. Finally, we show that a defect in protein glycosylation is a major reason for cell wall instability of RNA exosome mutants. Genes encoding enzymes that act in the early steps of the protein glycosylation pathway are downregulated at high temperature in cells lacking Rrp6 protein or Dis3 exoribonuclease activity and overexpression of the essential enzyme Psa1, that catalyzes synthesis of the mannosylation precursor, suppresses temperature sensitivity and aberrant morphology of these cells. Furthermore, this defect is connected to a temperature-dependent increase in accumulation of non-coding RNAs transcribed from loci encoding relevant glycosylation-related genes.

核RNA外泌体是真核细胞中主要的3'→5'RNA降解和加工复合物，其失调因此影响基因表达和活力。在这项工作中，我们表明 RNA 外泌体活性对于维持酿酒酵母细胞壁的稳定性是必需的。虽然必需的 RNA 外泌体催化亚基 Dis3 提供核糖核酸外切酶催化活性，但第二个催化亚基 Rrp6 在此过程中具有非催化作用。 RNA 外泌体辅助因子 Rrp47 和 Air1/2 也参与其中。 RNA外泌体突变体在用细胞壁应激物处理后在高温或生理温度下经历渗透介质细胞裂解。最后，我们发现蛋白质糖基化缺陷是RNA外泌体突变体细胞壁不稳定的主要原因。在缺乏 Rrp6 蛋白或 Dis3 核糖核酸外切酶活性以及必需酶 Psa1 过度表达的细胞中，编码在蛋白质糖基化途径早期步骤中起作用的酶的基因在高温下下调，Psa1 催化甘露糖基化前体的合成，抑制温度敏感性和异常形态这些细胞。此外，这种缺陷与从编码相关糖基化相关基因的基因座转录的非编码RNA积累的温度依赖性增加有关。