CAN1 Arginine Permease Deficiency Extends Yeast Replicative Lifespan via Translational Activation of Stress Response Genes

Transcriptional regulation plays an important role in the control of gene expression during aging. However, translation efficiency likely plays an equally important role in determining protein abundance, but has been relatively under studied in this context. Here we used RNA-seq and ribosome profiling to investigate the role of translational regulation in lifespan extension by CAN1 gene deletion in yeast. Through comparison of the transcriptional and translational changes in cells lacking CAN1 with other long-lived mutants, we were able to identify critical regulatory factors, including transcription factors and mRNA-binding proteins, that coordinate transcriptional and translational responses. Together, our data support a model in which deletion of CAN1 extends replicative lifespan through increased translation of proteins that facilitate cellular response to stress. This study extends our understanding of the importance of translational control in regulating stress resistance and longevity.转录调控（transcriptional regulation）在衰老过程中的基因表达调控中发挥重要作用。然而，翻译效率在决定蛋白质丰度方面或许同样扮演着关键角色，但在衰老研究的相关语境下，该领域迄今仍相对缺乏深入探讨。本研究借助RNA测序（RNA-seq）与核糖体谱分析（ribosome profiling）技术，探究了酿酒酵母中CAN1基因（CAN1 gene）缺失所介导的寿命延长过程中，翻译调控所发挥的作用。通过将CAN1缺失细胞的转录与翻译变化与其他长寿突变体进行对比分析，本研究成功鉴定出一批关键调控因子，包括协同调控转录与翻译应答的转录因子及mRNA结合蛋白。综合而言，本研究数据支持如下模型：CAN1基因缺失通过提升促进细胞应激应答的蛋白质的翻译水平，从而延长了酵母的复制型寿命。本研究加深了学界对翻译调控在调控应激抗性与寿命过程中重要性的认知。