Longevity & AgingRNA Sugar Coating Hides Self-RNA from Immune Attacks and Enables Silent Cell Cleanup
Researchers discovered that small RNAs carry sugar-based N-glycan modifications that conceal a hypermodified base (acp³U), preventing the immune system from mistakenly attacking the body's own RNA. When these glycans were enzymatically stripped away, purified small RNAs—including those circulating in human and mouse blood—triggered potent type I interferon and inflammatory cytokine responses through TLR3 and TLR7 receptors. Critically, this glycan shield also enables the silent, non-inflammatory clearance of dying cells (efferocytosis): apoptotic cells with their RNA glycans intact are engulfed quietly, while de-glycosylated apoptotic cells spark inflammatory signaling. Genetically deleting DTWD2, the enzyme that creates acp³U, abolished immune activation, confirming acp³U as the immunostimulatory trigger unmasked by glycan removal.
