论文标题

转录翻译耦合中的随机动力学和核糖体-RNAP相互作用

Stochastic dynamics and ribosome-RNAP interactions in Transcription-Translation Coupling

论文作者

Li, Xiangting, Chou, Tom

论文摘要

在某些细胞条件下,原核生物中的转录和mRNA翻译似乎是“耦合的”,其中mRNA转录物的形成和其相关蛋白的产生在时间上相关。这种转录翻译耦合(TTC)已被唤起作为一种速度加快整体过程,在转录过程中提供保护和/或调节转录和蛋白质形成的时间的机制。什么分子机制是核糖体-RNAP耦合的基础,以及如何执行这些功能,尚未明确建模。我们开发和分析了连续的随机模型,该模型结合了核糖体和RNAP伸长率,起始和终止速率,rNAP暂停以及直接核糖体和RNAP相互作用(排除和结合)。我们的模型预测延迟时间的分布如何取决于转录和翻译的这些分子特征。我们还提出了TTC的其他措施:直接的核糖体-RNAP结合概率和时间的比例,翻译转录过程受到转录终止蛋白的攻击。这些指标量化了TTC的不同方面,并差异取决于已知分子过程的参数。我们使用我们的指标来揭示模型如何以及何时可以表现出转录的加速度或减速性,以及防止终止。我们的详细机械模型为设计新的实验测定方法提供了一个基础,以更好地阐明TTC的机制。

Under certain cellular conditions, transcription and mRNA translation in prokaryotes appear to be "coupled," in which the formation of mRNA transcript and production of its associated protein are temporally correlated. Such transcription-translation coupling (TTC) has been evoked as a mechanism that speeds up the overall process, provides protection during the transcription, and/or regulates the timing of transcript and protein formation. What molecular mechanisms underlie ribosome-RNAP coupling and how they can perform these functions have not been explicitly modeled. We develop and analyze a continuous-time stochastic model that incorporates ribosome and RNAP elongation rates, initiation and termination rates, RNAP pausing, and direct ribosome and RNAP interactions (exclusion and binding). Our model predicts how distributions of delay times depend on these molecular features of transcription and translation. We also propose additional measures for TTC: a direct ribosome-RNAP binding probability and the fraction of time the translation-transcription process is "protected" from attack by transcription-terminating proteins. These metrics quantify different aspects of TTC and differentially depend on parameters of known molecular processes. We use our metrics to reveal how and when our model can exhibit either acceleration or deceleration of transcription, as well as protection from termination. Our detailed mechanistic model provides a basis for designing new experimental assays that can better elucidate the mechanisms of TTC.

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