Small aptamer-based regulatory devices can be designed to control a range of RNA-dependent cellular processes and emerged as promising tools for fine-tuning gene expression in synthetic biology. Here, we design a conceptually new riboswitch device that allows for the conditional regulation of polyadenylation. By making use of ligand-induced sequence occlusion, the system efficiently controls the accessibility of the eukaryotic polyadenylation signal. Undesirable 3′-extended read-through products are counteracted by the downstream insertion of a microRNA target site. We demonstrate the modularity of the system with regard to sensor aptamers and polyadenylation signals used and combine the newly designed riboswitch with well-known aptazymes to yield superior composite systems. In addition, we show that the switches can be used to control alternative polyadenylation. The presented genetic switches require very little coding space and can be easily optimized by rational adjustments of the thermodynamic stability. The polyadenylation riboswitch extends the repertoire of RNA-based regulators and opens new possibilities for the generation of complex synthetic circuits.

中文翻译：

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适体介导的多聚腺苷酸化调控哺乳动物细胞基因表达调控

基于适体的小型调控装置可设计用于控制一系列依赖于 RNA 的细胞过程，并成为微调合成生物学中基因表达的有前途的工具。在这里，我们设计了一种概念上新的核糖开关装置，允许有条件地调节多聚腺苷酸化。通过利用配体诱导的序列闭塞，该系统有效地控制了真核聚腺苷酸化信号的可及性。不需要的 3' 延伸通读产物被下游插入的 microRNA 靶位点抵消。我们展示了系统在使用的传感器适体和聚腺苷酸化信号方面的模块化，并将新设计的核糖开关与众所周知的适体酶相结合，以产生卓越的复合系统。此外，我们表明开关可用于控制替代聚腺苷酸化。所提出的基因开关需要很少的编码空间，并且可以通过热力学稳定性的合理调整轻松优化。多聚腺苷酸化核糖开关扩展了基于 RNA 的调节剂的库，并为生成复杂的合成电路开辟了新的可能性。