Multifarious translational regulation during replicative aging in yeast

Protein synthesis is strictly regulated during replicative aging in yeast, but global translational regulation during replicative aging is poorly characterized. To conduct ribosomal profiling during replicative aging, we collected a large number of dividing aged cells using a miniature chemostat aging device. Translational efficiency, defined as the number of ribosome footprints normalized to transcript abundance, was compared between young and aged cells for each gene. We identified more than 700 genes with changes greater than twofold during replicative aging. Increased translational efficiency was observed in genes involved in DNA repair and chromosome organization. Decreased translational efficiency was observed in genes encoding ribosome components, transposon Ty1 and Ty2 genes, transcription factor HAC1 genes associated with the unfolded protein response, genes involved in cell wall synthesis and assembly, and ammonium permease genes. Our results provide a global view of translational regulation during replicative aging, in which the pathways involved in various cell functions are translationally regulated and cause diverse phenotypic changes.酵母（yeast）复制性衰老过程中蛋白质合成受到严格调控，但目前学界对复制性衰老过程中的全局翻译调控机制尚缺乏充分表征。为开展复制性衰老过程中的核糖体谱分析（ribosomal profiling），我们借助微型恒化器衰老装置（chemostat aging device），收集了大量处于分裂状态的衰老酵母细胞。翻译效率（translational efficiency）被定义为经转录本丰度标准化后的核糖体足迹（ribosome footprints）数量，本研究以此指标对每个基因的年轻与衰老细胞样本进行了比较。我们共鉴定出700余个在复制性衰老过程中翻译效率变化幅度超过两倍的基因。其中，参与DNA修复与染色体组织过程的基因，其翻译效率显著上调。而编码核糖体组分的基因、转座子Ty1与Ty2基因、关联未折叠蛋白反应（unfolded protein response）的转录因子HAC1基因、参与细胞壁合成与组装的基因，以及铵通透酶基因的翻译效率则显著下调。本研究结果阐明了复制性衰老过程中翻译调控的全局图景：涉及各类细胞功能的通路均受到翻译层面的调控，并由此引发多样化的表型改变。