Targeting DEAD‐box RNA helicases: The emergence of molecular staples

RNA helicases constitute a large family of proteins that play critical roles in mediating RNA function. They have been implicated in all facets of gene expression pathways involving RNA, from transcription to processing, transport and translation, and storage and decay. There is significant interest in developing small molecule inhibitors to RNA helicases as some family members have been documented to be dysregulated in neurological and neurodevelopment disorders, as well as in cancers. Although different functional properties of RNA helicases offer multiple opportunities for small molecule development, molecular staples have recently come to the forefront. These bifunctional molecules interact with both protein and RNA components to lock them together, thereby imparting novel gain‐of‐function properties to their targets. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule‐RNA Interactions RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications Potent inhibitors of RNA helicases have emerged that act as molecular staples—interacting with both the helicase target and RNA. By stabilizing RNA‐bound helicases they impart gain‐of‐function properties to their targets to disrupt activity.