The one-message-per-cell-cycle rule: A conserved minimum transcription level for essential genes.
The one-message-per-cell-cycle rule: A conserved minimum transcription level for essential genes.
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DOI：
10.1101/2023.07.06.548020
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发表时间：
2023-07-07
期刊：
影响因子：
--
通讯作者：
Wiggins PA
中科院分区：
文献类型：
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作者：
Lo TW;Choi HKJ;Huang D;Wiggins PA
细胞过程固有的随机性导致细胞间蛋白质丰度的显著差异。虽然已经对这种噪声进行了描述和建模，但其更广泛的影响和意义仍不清楚。在本文中，我们回顾了噪声模型，并将每个细胞周期转录的消息数量确定为噪声的关键决定因素。在酵母中，我们证明了这个量可以用蛋白质丰度来预测噪声的非规范标度，也可以定量地预测其大小。然后，我们假设生长稳健性要求对必要基因表达的噪音有一个上限，对应于转录水平的下限。我们证明了这样一个底线的存在：在三种模式生物之间，每个细胞周期一个消息的最低转录水平是保守的：大肠杆菌、酵母和人类。此外，所有这三种生物在每个细胞周期中，每个基因转录的消息数量都相同。这个常见的转录程序揭示了对噪音的稳健性在决定大部分必需基因的表达水平方面发挥了核心作用，并且这一基本的最优策略从大肠杆菌到人类细胞都是保守的。
The inherent stochasticity of cellular processes leads to significant cell-to-cell variation in protein abundance. Although this noise has already been characterized and modeled, its broader implications and significance remain unclear. In this paper, we revisit the noise model and identify the number of messages transcribed per cell cycle as the critical determinant of noise. In yeast, we demonstrate that this quantity predicts the non-canonical scaling of noise with protein abundance, as well as quantitatively predicting its magnitude. We then hypothesize that growth robustness requires an upper ceiling on noise for the expression of essential genes, corresponding to a lower floor on the transcription level. We show that just such a floor exists: a minimum transcription level of one message per cell cycle is conserved between three model organisms: Escherichia coli, yeast, and human. Furthermore, all three organisms transcribe the same number of messages per gene, per cell cycle. This common transcriptional program reveals that robustness to noise plays a central role in determining the expression level of a large fraction of essential genes, and that this fundamental optimal strategy is conserved from E. coli to human cells.