RNA Compensation: A Positive Feedback Insulation Strategy for RNA-Based Transcription Networks
RNA Compensation: A Positive Feedback Insulation Strategy for RNA-Based Transcription Networks
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DOI：
10.1021/acssynbio.1c00540
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发表时间：
2022-03-18
影响因子：
4.7
通讯作者：
Franco, Elisa
中科院分区：
文献类型：
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作者：
Liu, Baiyang;Samaniego, Christian Cuba;Franco, Elisa
生物分子系统信号模块化的缺乏对复杂网络的工程设计提出了重大挑战。上游和下游电路之间的定向信号需要结合事件的存在，这会导致调节分子的消耗，并可能危及上游电路的运行。这个问题之前已经通过引入包括高增益负反馈和激活-失活反应周期的绝缘策略来解决。在本文中，我们专注于基于RNA的电路，并提出了一种新的正反馈策略，以减轻我们提出的由于RNA输入与RNA靶标的不可逆结合而导致的每个调控事件的信号消耗。为了缓解这一问题，在转录输出的同时添加额外的RNA输入来补偿RNA消耗，无论下游模块的数量如何，输入RNA分子的浓度都保持稳定。我们将这种策略称为RNA补偿，它可以应用于具有严格输入输出增益的系统，例如小转录激活RNA （STARs）。我们的理论分析表明，RNA补偿不仅消除了单个基于STAR的调控因子的信号消耗，而且还提高了STAR级联的可组合性和RNA双稳态系统的模块化。
The lack of signaling modularity of biomolecular systems poses major challenges toward engineering complex networks. Directional signaling between an upstream and a downstream circuit requires the presence of binding events, which result in the consumption of regulatory molecules and can compromise the operation of the upstream circuit. This issue has been previously addressed by introducing insulation strategies that include high-gain negative feedback and activation-deactivation reaction cycles. In this paper, we focus on RNA-based circuits and propose a new positive-feedback strategy to mitigate signal consumption that we propose occurs for each regulatory event due to irreversible binding of the RNA input to the RNA target. To mitigate this, an extra RNA input is added in tandem with transcription output to compensate the RNA consumption, leading to concentration robustness of the input RNA molecule regardless of the amount of downstream modules. We term this strategy RNA compensation, and it can be applied to systems that have a stringent input-output gain, such as Small Transcription Activating RNAs (STARs). Our theoretical analysis shows that RNA compensation not only eliminates the signaling consumption in individual STAR-based regulators, but also improves the composability of STAR cascades and the modularity of RNA bistable systems.