There is a high demand to develop chemical tools to control the property and function of
RNA. Current methods mainly rely on ultraviolet light-based caging strategies, which may cause
phototoxicity in live cell-based experiments. We herein report an endogenous stimulus-responsive
RNA acylation approach by introducing boronate
ester (BE) groups to 2'-hydroxyls through postsynthetic modification. Treatment with
hydrogen peroxide (H2O2) yields a
phenol derivative which undergoes a 1,6-eliminaton for the traceless release of 2'-hydroxyl. We demonstrated that the acylation of
crRNA enabled conditional regulation of CRISPR/Cas13a activity for activatable detection of target
RNA. We also showed that the highly specific acylation of the single
RNA in 8-17
DNAzyme allowed reversible control of the catalytic activity of
DNAzyme, which was further applied to the cell-selective imaging of
metal ions in
cancer cells. Thus, our strategy provides a simple, general, and cell-selective method to control
RNA activity, affording great potential in the construction of activatable
RNA sensors and pre-
RNA medicines.