Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK.
FEMS Yeast Res. 2019 Mar 1;19(2). doi: 10.1093/femsyr/foz014.
Topological analysis of large networks, which focus on a specific biological process or on related biological processes, where functional coherence exists among the interacting members, may provide a wealth of insight into cellular functionality. This work presents an unbiased systems approach to analyze genetic, transcriptional regulatory and physical interaction networks of yeast genes possessing such functional coherence to gain novel biological insight. The present analysis identified only a few transcriptional regulators amongst a large gene cohort associated with the protein metabolism and processing in yeast. These transcription factors are not functionally required for the maintenance of these tasks in growing cells. Rather, they are involved in rewiring gene transcription in response to such major challenges as starvation, hypoxia, DNA damage, heat shock or the accumulation of unfolded proteins. Indeed, only a subset of these proteins were captured empirically in the nuclear-enriched fraction of non-stressed yeast cells, suggesting that the transcriptional regulation of protein metabolism and processing in yeast is primarily concerned with maintaining cellular robustness in the face of threat by either internal or external stressors.
对关注特定生物过程或相关生物过程的大型网络进行拓扑分析，其中相互作用的成员之间存在功能一致性，这可能为细胞功能提供丰富的见解。本工作采用无偏的系统方法来分析具有这种功能一致性的酵母基因的遗传、转录调控和物理相互作用网络，以获得新的生物学见解。目前的分析仅在与酵母中蛋白质代谢和加工相关的大量基因群体中鉴定出少数几个转录调节剂。这些转录因子对于维持生长细胞中这些任务的进行并非必需。相反，它们参与重编基因转录，以响应饥饿、缺氧、DNA 损伤、热休克或未折叠蛋白积累等主要挑战。事实上，只有这些蛋白质中的一小部分被经验性地捕获在非应激酵母细胞的核富集部分中，这表明酵母中蛋白质代谢和加工的转录调控主要涉及在内部或外部胁迫威胁下维持细胞的稳健性。
