核糖体自组装导致重叠的繁殖周期并提高生长速度
Ribosome self-assembly leads to overlapping reproduction cycles and increases growth rate
摘要：
在宽松的环境中，E.大肠杆菌的干物质每21分钟就增加一倍。在此期间，核糖体、RNA聚合酶和蛋白质组都加倍。然而，如何将细菌倍增时间与生长过程中的其他生物学相关时间尺度联系起来的问题仍然是虚幻的，这是由于这些过程的复杂的时间嵌套模式。特别是，细胞倍增时间和核糖体组装时间之间的关系尚不清楚。在这里，我们开发了一个模型，将生长速率与核糖体组装时间联系起来，并表明自组装步骤的存在增加了整体生长速率，因为在核糖体自组装过程中，现有的核糖体可以通过在前一轮完成之前制造新一批核糖体蛋白质来开始新一轮的繁殖。核糖体繁殖周期的重叠增加了生长速率，超过了通常假设的连续限制。使用最近的数据从核糖体分析和众所周知的测量的平均翻译速率，刚性的边界上的体内核糖体自组装时间设置，这是鲁棒的假设有关的生物噪声。在21分钟的倍增时间，核糖体组装时间被发现约为6分钟-比通常估计的大三倍。我们进一步使用我们的模型来解释最近发现的核糖体组装抑制剂药物的不利影响，并预测限制核糖体组装分子伴侣的表达对整体生长速率的影响。
英文摘要：
In permissive environments, E. coli can double its dry mass every 21 minutes. During this time, ribosomes, RNA polymerases, and the proteome are all doubled. Yet, the question of how to relate bacterial doubling time to other biologically relevant time scales in the growth process remains illusive, due to the complex temporal nesting pattern of these processes. In particular, the relation between the cell's doubling time and the ribosome assembly time is not known. Here we develop a model that connects growth rate to ribosome assembly time and show that the existence of a self-assembly step increases the overall growth rate, because during ribosome self-assembly existing ribosomes can start a new round of reproduction, by making a new batch of ribosomal proteins prior to the completion of the previous round. This overlapping of ribosome reproduction cycles increases growth rate beyond the serial-limit that is typically assumed to hold. Using recent data from ribosome profiling and well known measurements of the average translation rate, rigid bounds on the in-vivo ribosome self-assembly time are set, which are robust to the assumptions regarding the biological noises involved. At 21 minutes doubling time, the ribosome assembly time is found to be approximately 6 minutes --- three fold larger than the common estimate. We further use our model to explain the detrimental effect of a recently discovered ribosome assembly inhibitor drug, and predict the effect of limiting the expression of ribosome assembly chaperons on the overall growth rate.
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