Discovering glycoRNA: Traditional and Non‐Canonical Approaches to Studying RNA Modifications

Abstract Chemical biology opens the door to understanding biological processes in many areas, but nowhere has it had a greater impact on defining a field than in glycobiology. The Wolf and Nobel Prize‐winning work by Carolyn Bertozzi and coworkers to conceptualize bioorthogonal chemistry, enable it on living cells, deploy it with metabolic chemical reporters (MCRs) such as N‐azidoacetylmannosamine‐tetraacylated (Ac 4 ManNAz), has allowed researchers to elucidate the structure, functions, and regulation of complex glycans across various domains of life. In this review, we highlight how our work using Ac 4 ManNAz to discover glycosylated RNA (glycoRNA) shed the traditional paradigms of RNA post‐transcriptional modification discovery. While our understanding of RNA modifications has historically been expanded with unbiased chemical tools, the creative use of Ac 4 ManNAz for the targeted study of RNA's intersection with glycobiology has advanced Bertozzi's impact into the world of RNA.