A Light‐Controllable Chemical Modulation of m<sup>6</sup>A RNA Methylation
Lan Ling, Yingjie Sun, Xiaoyang Jin, Li‐Jun Xie, Li Liu, Liang Cheng
Abstract
Abstract Bioactive small molecules with photo‐removable protecting groups have provided spatial and temporal control of corresponding biological effects. We present the design, synthesis, computational and experimental evaluation of the first photo‐activatable small‐molecule methyltransferase agonist. By blocking the functional N‐H group on MPCH with a photo‐removable ortho‐nitrobenzyl moiety, we have developed a promising photo‐caged compound that had completely concealed its biological activity. Short UV light exposure of cells treated with that caged molecule in a few minutes resulted in a considerable hypermethylation of m 6 A modification in transcriptome RNAs, implicating a rapid release of the parent active compound. This study validates for the first time the photo‐activatable small organic molecular concept in the field of RNA epigenetic research, which represents a novel tool in spatiotemporal and cellular modulation approaches.