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.

RNA是一种多功能生物分子，具有广泛的生物功能，远远超出了其最初描述的作为简单信息载体的作用。控制、操纵和修饰 RNA 的化学方法的发展有可能对其许多功能和特性产生新的见解。传统上，大多数这些方法涉及使用固态合成或酶促转化对 RNA 结构进行化学修饰。然而，在过去的 15 年里，通过选择性酰化 2'-羟基 (2'-OH) 基团对 RNA 进行直接功能化已成为一种强大的替代方案，可以对合成和转录的 RNA 进行简单修饰。在这篇综述中，我们讨论了 RNA 2'-OH 酰化的有效试剂的化学性质和设计，强调了在水存在下 2'-OH 反应性的独特问题。我们详细阐述了如何利用 RNA 2'-OH 酰化来开发选择性化学探针，以探究 RNA 的结构和功能，并描述该领域的新发展和应用。