Dohno Chikara, Kimura Maki, Fujiwara Yusuke, Nakatani Kazuhiko
Department of Regulatory Bioorganic Chemistry, SANKEN (The Institute of Scientific and Industrial Research), Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
Nucleic Acids Res. 2023 Oct 13;51(18):9533-9541. doi: 10.1093/nar/gkad690.
Single-stranded RNA folds into a variety of secondary and higher-order structures. Distributions and dynamics of multiple RNA conformations are responsible for the biological function of RNA. We here developed a photoswitchable molecular glue for RNA, which could reversibly control the association of two unpaired RNA regions in response to light stimuli. The photoswitchable molecular glue, NCTA, is an RNA-binding ligand possessing a photoisomerizable azobenzene moiety. Z-NCTA is an active ligand for the target RNA containing 5'-WGG-3'/5'-WGG-3' (W = U or A) site and stabilizes its hybridized state, while its isomer E-NCTA is not. Photoreversible isomerization of NCTA enabled control of the secondary and tertiary structure of the target RNA. The RNA-cleaving activity of hammerhead ribozyme, where appropriate RNA folding is necessary, could be reversibly regulated by photoirradiation in cells treated with NCTA, demonstrating precise photocontrol of RNA structure and function by the photoswitchable molecular glue.
单链RNA折叠成各种二级和高级结构。多种RNA构象的分布和动态变化决定了RNA的生物学功能。我们在此开发了一种用于RNA的光开关分子胶水，它可以响应光刺激可逆地控制两个未配对RNA区域的结合。这种光开关分子胶水NCTA是一种具有光异构化偶氮苯部分的RNA结合配体。Z-NCTA是针对含有5'-WGG-3'/5'-WGG-3'（W = U或A）位点的靶RNA的活性配体，并能稳定其杂交状态，而其异构体E-NCTA则不然。NCTA的光可逆异构化能够控制靶RNA的二级和三级结构。锤头状核酶的RNA切割活性（其中适当的RNA折叠是必需的）在用NCTA处理的细胞中可通过光照射进行可逆调节，这证明了这种光开关分子胶水对RNA结构和功能的精确光控。
