Cell surface RNAs define a new interface for immune recognition.

Cell surface glycoRNAs have recently emerged as an unexpected class of RNA-glycan conjugates. Their discovery challenges the long-standing view that RNA is confined to intracellular compartments. These small noncoding RNAs, modified with N- or O-linked glycans and displayed on the outer leaflet of the plasma membrane, create a unique molecular interface recognizable by both glycan-binding and nucleic acid-sensing immune receptors. Recent studies suggest that glycoRNAs engage multiple immune receptor families, including P-selectin, Siglecs, Toll-like receptors (TLRs), and lectins, to influence neutrophil trafficking, immune activation, and tolerance. For instance, interactions between P-selectin and glycoRNAs have been implicated in neutrophil recruitment. In this Mini-Review, we summarize current knowledge of the molecular features of glycoRNAs and their emerging interfaces with immune receptors and discuss how glycoRNAs may represent a new layer of immune regulation at the cell surface.