Molecular Glue for RNA: Regulating RNA Structure and Function through Synthetic RNA Binding Molecules

We introduce the concept of molecular glues for RNA, in which specific RNA‐binding small molecules induce designed structural changes in target functional RNAs, resulting in modulation of the functions. (Z)‐NCTS is an RNA‐mismatch‐binding small molecule that recognizes 5′‐r(XGG)‐3′/5′‐r(XGG)‐3′ sequences (X=U or A) and acts as a molecular glue for RNA. The binding of (Z)‐NCTS brings two distinct 5′‐r(XGG)‐3′ domains into contact with each other, and this can result in higher‐order structural changes of target RNAs. We applied (Z)‐NCTS to induce the formation of a proposed tertiary structure of a ribozyme together with activation of RNA‐cleaving ability. The concept of a molecular glue could inspire new small‐molecule‐based strategies for regulating biological functions: a synthetic small molecule targeting functional RNAs could regulate the RNA structure and function. Let′s stick together: We introduce the concept of molecular glues for RNA. Specific RNA‐binding small‐molecule compounds are used to induce particular structural change in target functional RNAs, resulting in modulation of their functions.