Reversible Control of RNA Splicing by Photoswitchable Small Molecules
Reversible Control of RNA Splicing by Photoswitchable Small Molecules
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DOI：
10.1021/jacs.3c03275
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发表时间：
2023-06-05
影响因子：
15
通讯作者：
Vazquez，Olalla
中科院分区：
文献类型：
--
作者：
Zhang，Lei;Xie，Xiulan;Vazquez，Olalla
动力学是RNA功能和结构所固有的。然而，精确地提供基于rna的过程的时空分辨率的可用手段是稀缺的。在这里，我们的工作开创了一种可逆的方法，通过合成光开关来调节原代患者来源细胞内的RNA剪接。我们的小分子能够在mRNA和蛋白质水平上进行有条件的实时控制。核磁共振实验，连同理论计算、光化学表征、荧光偏振测量和基于活细胞的分析，证实了光依赖性外显子包涵以及目标功能蛋白的增加。因此，我们首先展示了光药理学调节剪接的潜力，调整了当前的光化学工具箱。将RNA研究整合为治疗创新的驱动力的及时性使我们的方法有望有助于重新绘制RNA的愿景。
Dynamics are intrinsic to both RNA function and structure. Yet, the available means to precisely provide RNA-based processes with spatiotemporal resolution are scarce. Here, our work pioneers a reversible approach to regulate RNA splicing within primary patient-derived cells by synthetic photoswitches. Our small molecule enables conditional real-time control at mRNA and protein levels. NMR experiments, together with theoretical calculations, photochemical characterization, fluorescence polarization measurements, and living cell-based assays, confirmed light-dependent exon inclusion as well as an increase in the target functional protein. Therefore, we first demonstrated the potential of photopharmacology modulation in splicing, tweaking the current optochemical toolkit. The timeliness on the consolidation of RNA research as the driving force toward therapeutical innovation holds the promise that our approach will contribute to redrawing the vision of RNA.