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基于 DNA-RNA-三链体的转录调控与分子逻辑门的整合。

Integration of DNA-RNA-triplex-based regulation of transcription into molecular logic gates.

机构信息

Department of Comparative Biomedicine and Food Science, University of Padova, Legnaro, Italy.

Physik Department, Technische Universitat München, Garching bei München, Germany.

出版信息

FEBS Lett. 2023 Oct;597(19):2461-2472. doi: 10.1002/1873-3468.14721. Epub 2023 Aug 31.

Abstract

In recent years, increasing numbers of noncoding RNA molecules were identified as possible components of endogenous DNA-RNA hybrid triplexes involved in gene regulation. Triplexes are potentially involved in complex molecular signaling networks that, if understood, would allow the engineering of biological computing components. Here, by making use of the enhancing and inhibiting effects of such triplexes, we demonstrate in vitro the construction of triplex-based molecular gates: 'exclusive OR' (XOR), 'exclusive NOT-OR' (XNOR), and a threshold gate, via transcription of a fluorogenic RNA aptamer. Precise modulation was displayed by the biomolecular-integrated systems over a wide interval of transcriptional outputs, ranging from drastic inhibition to significant enhancement. The present contribution represents a first example of molecular gates developed using DNA-RNA triplex nanostructures.

摘要

近年来,越来越多的非编码 RNA 分子被鉴定为可能的内源性 DNA-RNA 杂交三链体的组成部分,参与基因调控。三链体可能参与复杂的分子信号网络,如果能够理解这些网络,就可以设计生物计算组件。在这里,我们通过利用三链体的增强和抑制效应,在体外展示了基于三链体的分子门的构建:“异或”(XOR)、“异或非”(XNOR)和阈值门,通过荧光 RNA 适体的转录。生物分子集成系统在从强烈抑制到显著增强的广泛转录输出范围内显示出精确的调制。本研究首次展示了使用 DNA-RNA 三链体纳米结构开发的分子门。

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