Regulation of protein synthesis during quiescence in bacteria

项目摘要 蛋白质合成在生长发育过程中受到转录和转录后精细调控。 细菌细胞。这样的机制确保蛋白质合成有效地与一种 当营养不受限制时，细胞迅速分裂。然而，大多数微生物生命存在于非 增殖的静止状态，能够在营养限制和应激状态下存活 环境。因此，静止细胞的需求与生长细胞有很大的不同，因为它们必须 最大限度地减少能源消耗，从而在潜在的扩展时间内最大化可用资源 句号。蛋白质合成是细胞中能量最密集的代谢过程，占AS的比例 高达细菌总能量消耗的70%。一直以来，许多细菌，如芽孢杆菌 众所周知，当枯草杆菌退出指数增长时，它们会大大减少蛋白质的合成。 然而，静止的细胞需要有效地利用有利条件的出现和 进行复苏，因此这种衰减需要迅速可逆。此外，由于核糖体 本身就是合成最耗能的大分子机器，必须保护它不受 任何退化的过程。而且，与平移衰减一样，这种保护必须兼容 当条件改善时，有效地重新启动蛋白质合成。因此，无论是抑制性的还是 保护机制需要迅速可逆。细胞如何平衡这两个目标是 这项研究提案的主题。首先，我们研究核糖体是如何防止降解的。 在新陈代谢条件下，从头核糖体的生物合成受到限制。第二，我们调查了一个 翻译失活的可逆机制，尤其是核苷酸的作用 (P)ppGpp。

Project Summary Protein synthesis is subject to elaborate transcriptional and post-transcriptional regulation in growing bacterial cells. Such mechanisms ensure that protein synthesis is efficiently coupled to the needs of a rapidly dividing cell when nutrients are not limiting. However, most microbial life exists in a non- proliferating state of quiescence that enables survival during nutrient limitation and in stressful environments. Thus, the needs of quiescent cells are rather different from growing cells as they must minimize energy consumption so as to maximize available resources over a potentially extended period. Protein synthesis is the most energy intensive metabolic process in a cell, accounting for as much as ~70% of total energy consumption in bacteria. Consistently, many bacteria such as Bacillus subtilis are known to substantially reduce protein synthesis when they exit exponential growth. However, quiescent cells need to effectively exploit the emergence of favorable conditions and undergo resuscitation, so this attenuation needs to be rapidly reversible. In addition, as the ribosome is itself the most energetically costly macromolecular machine to synthesize, it must be protected from any degradative processes. And, as with translational attenuation, this protection must be compatible with efficient re-initiation of protein synthesis when conditions improve. Thus, both the inhibitory and protective mechanisms need to be quickly reversible. How the cell balances these two goals is the subject of this research proposal. First, we examine how ribosomes are protected from degradation under metabolic conditions where de novo ribosome biosynthesis is limited. Second, we investigate a reversible mechanism of translation inactivation with particular focus on the role of the nucleotide (p)ppGpp.