The European Physical Journal E ( IF 1.8 ) Pub Date : 2021-04-19 , DOI: 10.1140/epje/s10189-021-00013-0 Swathi Tej 1 , Sutapa Mukherji 1, 2
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Abstract
Often in bacterial regulatory networks, small non-coding RNAs (sRNA) interact with several mRNA species. The competition among mRNAs for binding to the common pool of sRNA might lead to crosstalk between the mRNAs. This is similar to the competing endogenous RNA effect that leads to complex gene regulation with stabilized gene expression in Eukaryotes. Here, we study an sRNA-driven feed-forward loop (sFFL) where the top-tier regulator, an sRNA, translationally activates the target protein (TP) as well as a transcriptional activator of the TP through binding to the respective mRNAs. We show that the sRNA-mediated crosstalk between the two mRNA species enables the sFFL to function in three different regimes depending on the synthesis rate of the transcriptional activator mRNA. Of these three regimes, there exists a sensitive regime where the TP level shows interesting features depending on the precise mechanism of target translation. In the case of translation entirely from sRNA–mRNA bound complexes, the TP level becomes maximum around the sensitive regime. Through stochastic analysis and simulations, we show that relative fluctuations in the TP level is minimized here. For translation both from mRNA and sRNA–mRNA bound complexes, the target expression shows a threshold response across the sensitive regime.
Graphic abstract
中文翻译：
小RNA驱动的前馈环：通过sRNA介导的串扰微调蛋白质合成
抽象的
通常在细菌调节网络中，小非编码 RNA (sRNA) 与多种 mRNA 相互作用。 mRNA 之间对与公共 sRNA 池结合的竞争可能会导致 mRNA 之间的串扰。这类似于真核生物中竞争性内源 RNA 效应导致复杂的基因调控和稳定的基因表达。在这里，我们研究了 sRNA 驱动的前馈环 (sFFL)，其中顶级调节器 sRNA 通过与各自的 mRNA 结合来翻译激活靶蛋白 (TP) 以及 TP 的转录激活剂。我们表明，两种 mRNA 物种之间 sRNA 介导的串扰使 sFFL 能够根据转录激活剂 mRNA 的合成速率以三种不同的方式发挥作用。在这三个机制中，存在一个敏感机制，其中 TP 水平根据目标翻译的精确机制显示出有趣的特征。在完全从 sRNA-mRNA 结合复合物进行翻译的情况下，TP 水平在敏感区域附近变得最大。通过随机分析和模拟，我们表明TP水平的相对波动在这里被最小化。对于 mRNA 和 sRNA-mRNA 结合复合物的翻译，目标表达显示出跨敏感状态的阈值响应。
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