Cell surface RNAs control neutrophil recruitment

RNAs localizing to the outer cell surface have been recently identified in mammalian cells, including RNAs with glycan modifications known as glycoRNAs. However, the functional significance of cell surface RNAs and their production are poorly known. We report that cell surface RNAs are critical for neutrophil recruitment and that the mammalian homologs of the sid-1 RNA transporter are required for glycoRNA expression. Cell surface RNAs can be readily detected in murine neutrophils, the elimination of which substantially impairs neutrophil recruitment to inflammatory sites in vivo and reduces neutrophils’ adhesion to and migration through endothelial cells. Neutrophil glycoRNAs are predominantly on cell surface, important for neutrophil-endothelial interactions, and can be recognized by P-selectin (Selp). Knockdown of the murine Sidt genes abolishes neutrophil glycoRNAs and functionally mimics the loss of cell surface RNAs. Our data demonstrate the biological importance of cell surface glycoRNAs and highlight a noncanonical dimension of RNA-mediated cellular functions. [Display omitted] •GlycoRNAs are present in neutrophils and primarily locate on the cell surface•Cell surface RNAs facilitate neutrophil recruitment to inflammatory sites in vivo•Neutrophil glycoRNAs bind to P-selectin on endothelial cells•Sidt genes are required for glycoRNA expression and cell surface RNA function RNAs present on the outer cell surface have been recently identified in mammalian cells, but the functional significance of these cell surface RNAs hasn’t been clear. This study reveals roles of cell surface RNAs in mediating neutrophil recruitment to inflammatory sites in mice and the mechanisms regulating cell surface glycoRNA functions and levels.