The ability to tune RNA and gene expression dynamics is greatly needed for biotechnological applications. Native RNA stabilizers or engineered 5′ stability hairpins have been used to regulate transcript half-life to control recombinant protein expression. However, these methods have been mostly ad hoc and hence lack predictability and modularity. Here, we report a library of RNA modules called degradation-tuning RNAs (dtRNAs) that can increase or decrease transcript stability in vivo and in vitro. dtRNAs enable modulation of transcript stability over a 40-fold dynamic range in Escherichia coli with minimal influence on translation initiation. We harness dtRNAs in messenger RNAs and noncoding RNAs to tune gene circuit dynamics and enhance CRISPR interference in vivo. Use of stabilizing dtRNAs in cell-free transcription-translation reactions also tunes gene and RNA aptamer production. Finally, we combine dtRNAs with toehold switch sensors to enhance the performance of paper-based norovirus diagnostics, illustrating the potential of dtRNAs for biotechnological applications.

生物技术应用非常需要调整 RNA 和基因表达动力学的能力。天然 RNA 稳定剂或工程化的 5' 稳定性发夹已被用于调节转录本半衰期以控制重组蛋白表达。然而，这些方法大多是临时的，因此缺乏可预测性和模块化。在这里，我们报告了一个称为降解调节 RNA (dtRNA) 的 RNA 模块库，它可以增加或降低体内和体外的转录本稳定性。dtRNA 能够在大肠杆菌中调节超过 40 倍动态范围的转录物稳定性对翻译启动的影响最小。我们利用信使 RNA 和非编码 RNA 中的 dtRNA 来调节基因电路动力学并增强体内 CRISPR 干扰。在无细胞转录-翻译反应中使用稳定的 dtRNA 也可以调节基因和 RNA 适体的产生。最后，我们将 dtRNA 与脚趾开关传感器相结合，以提高基于纸质的诺如病毒诊断的性能，展示了 dtRNA 在生物技术应用中的潜力。