Rationalizing Context-Dependent Performance of Dynamic RNA Regulatory Devices.
Rationalizing Context-Dependent Performance of Dynamic RNA Regulatory Devices.
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合理化动态 RNA 调节装置的上下文相关性能。
DOI：
10.1021/acssynbio.8b00041
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发表时间：
2018
影响因子：
4.7
通讯作者：
Kent R
中科院分区：
文献类型：
--
作者：
Kent R
RNA感知、调节和储存信息的能力对于各种功能应用（包括用于合成生物学的调节控制装置的开发）是有吸引力的属性。已知RNA折叠和功能是高度环境敏感的，这限制了RNA调控装置的模块化和重复使用以控制不同的异源序列和基因。我们通过构建和筛选N端同义密码子变异体文库，探讨了位于5′ UTR的翻译ON核糖开关的序列上下文敏感性的原因和影响。通过改变N-末端密码子的使用，我们能够获得具有广泛功能性能特性（ON、OFF、倍数变化）的RNA装置。线性回归和计算的指标被用来合理化的主要决定功能，导致最佳的核糖开关性能，并确定多个解释性指标之间的相互作用。最后，偏最小二乘（PLS）分析，以了解指标和它们各自的性能影响。这个PLS模型被证明是我们的图书馆提供了很好的解释。这项研究提供了一个新的多变量分析框架，以合理化密码子上下文性能的变构RNA装置。该框架也将作为一个平台，为未来的核糖开关上下文工程的努力。
The ability of RNA to sense, regulate, and store information is an attractive attribute for a variety of functional applications including the development of regulatory control devices for synthetic biology. RNA folding and function is known to be highly context sensitive, which limits the modularity and reuse of RNA regulatory devices to control different heterologous sequences and genes. We explored the cause and effect of sequence context sensitivity for translational ON riboswitches located in the 5′ UTR, by constructing and screening a library of N-terminal synonymous codon variants. By altering the N-terminal codon usage we were able to obtain RNA devices with a broad range of functional performance properties (ON, OFF, fold-change). Linear regression and calculated metrics were used to rationalize the major determining features leading to optimal riboswitch performance, and to identify multiple interactions between the explanatory metrics. Finally, partial least squared (PLS) analysis was employed in order to understand the metrics and their respective effect on performance. This PLS model was shown to provide good explanation of our library. This study provides a novel multivariant analysis framework to rationalize the codon context performance of allosteric RNA-devices. The framework will also serve as a platform for future riboswitch context engineering endeavors.
影响因子：
16
作者：
Quax TE;Claassens NJ;Söll D;van der Oost J
通讯作者：
van der Oost J
影响因子：
64.8
作者：
Reining, Anke;Nozinovic, Senada;Schwalbe, Harald
通讯作者：
Schwalbe, Harald
影响因子：
4.7
作者：
Beilstein, Kim;Wittmann, Alexander;Suess, Beatrix
通讯作者：
Suess, Beatrix