Short regulatory RNA molecules underpin gene expression and govern cellular state and physiology. To establish an alternative layer of control over these processes, we generated chimeric regulatory RNAs that interact reversibly and light-dependently with the light-oxygen-voltage photoreceptor PAL. By harnessing this interaction, the function of micro RNAs (miRs) and short hairpin (sh) RNAs in mammalian cells can be regulated in a spatiotemporally precise manner. The underlying strategy is generic and can be adapted to near-arbitrary target sequences. Owing to full genetic encodability, it establishes optoribogenetic control of cell state and physiology. The method stands to facilitate the non-invasive, reversible and spatiotemporally resolved study of regulatory RNAs and protein function in cellular and organismal environments.

短调节 RNA 分子支持基因表达并控制细胞状态和生理机能。为了建立对这些过程的替代控制层，我们生成了与光-氧-电压光感受器 PAL 可逆和光依赖地相互作用的嵌合调节 RNA。通过利用这种相互作用，可以以时空精确的方式调节哺乳动物细胞中微 RNA (miR) 和短发夹 (sh) RNA 的功能。底层策略是通用的，可以适应近乎任意的目标序列。由于完全的遗传编码能力，它建立了细胞状态和生理学的光基因控制。该方法有助于对细胞和有机体环境中的调节 RNA 和蛋白质功能进行非侵入性、可逆和时空解析的研究。