The chemistry and applications of RNA 2'-OH acylation

RNA is a versatile biomolecule with a broad range of biological functions that go far beyond its initially described role as a simple information carrier. The development of chemical methods to control, manipulate and modify RNA has the potential to yield new insights into its many functions and properties. Traditionally, most of these methods involved the chemical modification of RNA structure using solid-state synthesis or enzymatic transformations. However, over the past 15 years, the direct functionalization of RNA by selective acylation of the 2'-hydroxyl (2'-OH) group has emerged as a powerful alternative that enables the simple modification of both synthetic and transcribed RNAs. In this Review, we discuss the chemical properties and design of effective reagents for RNA 2'-OH acylation, highlighting the unique problem of 2'-OH reactivity in the presence of water. We elaborate on how RNA 2'-OH acylation is being exploited to develop selective chemical probes that enable interrogation of RNA structure and function, and describe new developments and applications in the field.