Paul Avishek, Huang Jingyi, Han Yanxiao, Yang Xintong, Vuković Lela, Král Petr, Zheng Lifei, Herrmann Andreas
Zernike Institute for Advanced Materials, Dept. of Polymer Chemistry, University of Groningen Nijenborgh 4 9747 AG Groningen The Netherlands
DWI-Leibniz Institute for Interactive Materials Forckenbeckstr. 50 52056 Aachen Germany
Chem Sci. 2021 Jan 12;12(7):2646-2654. doi: 10.1039/d0sc05479h.
Controlling gene expression by light with fine spatiotemporal resolution not only allows understanding and manipulating fundamental biological processes but also fuels the development of novel therapeutic strategies. In complement to exploiting optogenetic tools, photochemical strategies mostly rely on the incorporation of photo-responsive small molecules into the corresponding biomacromolecular scaffolds. Therefore, generally large synthetic effort is required and the switching of gene expression in both directions within a single system remains a challenge. Here, we report a encoded ribo-switch, which consists of an engineered tRNA mimicking structure (TMS), under control of small photo-switchable signalling molecules. The signalling molecules consist of two amino glycoside molecules that are connected an azobenzene unit. The light responsiveness of our system originates from the photo-switchable noncovalent interactions between the signalling molecule and the TMS switch, leading to the demonstration of photochemically controlled expression of two different genes. We believe that this modular design will provide a powerful platform for controlling the expression of other functional proteins with high spatiotemporal resolution employing light as a stimulus.
以精细的时空分辨率通过光来控制基因表达，不仅有助于理解和操纵基本的生物学过程，还推动了新型治疗策略的发展。作为对光遗传学工具利用的补充，光化学策略主要依赖于将光响应小分子掺入相应的生物大分子支架中。因此，通常需要大量的合成工作，并且在单个系统中双向切换基因表达仍然是一个挑战。在此，我们报道了一种编码的核糖开关，它由一个模拟tRNA的工程结构（TMS）组成，受小型光开关信号分子的控制。这些信号分子由两个通过偶氮苯单元连接的氨基糖苷分子组成。我们系统的光响应性源于信号分子与TMS开关之间的光可切换非共价相互作用，从而实现了对两个不同基因的光化学控制表达的证明。我们相信，这种模块化设计将提供一个强大的平台，用于以光为刺激，以高时空分辨率控制其他功能蛋白的表达。
