Defining cell surface and glycosylated RNAs

The cell surface is a dynamic interface for biomolecular interactions, classically considered to be governed by proteins, lipids, and glycans. Advances in chemical biology and RNA detection have revealed that RNA molecules also reside at the cell surface. We initially identified a class of these resident RNAs as small noncoding RNAs covalently modified with N-glycans, termed glycoRNAs. In this review article, we discuss the technologies that have enabled the identification of glycoRNAs and the more general concept of cell surface RNAs. We also highlight emerging evidence for the trafficking of RNA to the extracellular space and the mechanisms that anchor RNA to the surface of living cells. These observations have reshaped our understanding of RNA regulatory mechanisms and encourage further investigation into previously unrecognized functions of RNAs.