AI 中文总结
研究细胞中mRNA翻译资源最优分配问题，利用动态数学模型网络，证明最优解有通用多折返结构，即编码区大部分区域转换速率高且均匀，边界附近低且变化，此结构适用于多种情况，可为细胞内电路设计提供指导。
AI 中文摘要
细胞中的mRNA翻译需要在多个转录本之间有效分配包括游离核糖体、tRNA分子和起始因子等共享且有限的资源。利用核糖体沿mRNA流动的动态数学模型网络，我们提出在所有转录本的所有翻译速率的总预算有限且共享的情况下，最大化细胞中总稳态蛋白质生产率的问题。我们证明，此资源分配问题的最优解具有多折返结构：在每个mRNA中，沿编码区大部分区域的转换速率高且近乎均匀，在mRNA边界附近较低且变化。我们的结果基于分层最优性的出现：无论资源如何在基因间分配，每个转录本内部应以基本相同的方式组织自身。这表明，要优化总体生产率，调节每个转录本的起始和终止区域就足够了。值得注意的是，这种通用的折返结构适用于任意数量的转录本、任意转录本长度和各种优化目标。这与观察到的保守翻译现象相符，如密码子梯度和起始主导调节。我们的发现也可为在翻译控制下运行的细胞内电路的合理设计提供指导。
英文摘要
mRNA translation in the cell requires efficient allocation of shared and limited resources including free ribosomes, tRNA molecules, and initiation factors across multiple transcripts. Using a network of dynamic mathematical models for ribosome flow along the mRNA, we pose the problem of maximizing the total steady-state protein production rate in the cell under a shared and limited total budget for all translation rates in all the transcripts. We prove that the optimal solution of this resource allocation problem admits a multi-turnpike structure: in each mRNA, the transition rates are high and nearly uniform along the bulk of the coding region, with lower and varying rates near the boundaries of the~mRNA. Our results are based on the emergence of hierarchical optimality: regardless of how resources are allocated among genes, every transcript should internally organize itself in essentially the same way. This suggests that to optimize the overall production rate it is sufficient to regulate the initiation and termination regions in each transcript. Remarkably, this universal turnpike structure holds for any number of transcripts, arbitrary transcript lengths, and various optimization criteria.This agrees with observed conserved translational phenomena, such as codon ramps and initiation-dominated regulation. Our findings may also provide guidelines for the rational design of intracellular circuits operating under translational control.
