Life and Medical Sciences (LIMES), University of Bonn, Gerhard-Domagk-Str.1, 53121, Bonn, Germany.
Lehrstuhl für Biochemie, Photobiochemie, University of Bayreuth, Universitätsstraße 30, 95440, Bayreuth, Germany.
Nat Commun. 2020 Sep 24;11(1):4825. doi: 10.1038/s41467-020-18673-5.
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.
短链调控 RNA 分子是基因表达的基础，能调控细胞状态和生理机能。为了给这些过程提供额外的控制层次，我们设计了嵌合调控 RNA，它们能与光氧电压型光感受器 PAL 进行可逆的、光依赖的相互作用。通过利用这种相互作用，我们可以在时空精确的方式调控哺乳动物细胞中 microRNA（miRs）和短发夹 RNA（shRNAs）的功能。这种底层策略具有通用性，可以适应几乎任意的靶序列。由于完全的遗传可编码性，它建立了细胞状态和生理机能的光电遗传控制。这种方法有望促进调控 RNA 和蛋白功能在细胞和机体环境中的非侵入性、可逆性和时空分辨研究。
