m6A methylation directs miRNA fate toward small extracellular vesicle export
Cells selectively export microRNAs (miRNAs) via small extracellular vesicles (sEVs), yet the molecular basis of this selectivity remains unclear. Here, we identify N6-methyladenosine (m6A) as a molecular signal that directs mature miRNA fate. m6A-modified miRNAs are preferentially enriched in sEVs, and METTL3-dependent methylation promotes export without altering total cellular levels. Disruption of the RRACH motif abolishes both m6A modification and export. Endogenous CRISPR editing demonstrates that m6A is required for physiological miRNA sorting. Mechanistically, YTHDC2 recognizes methylated miRNAs and cooperates with GW182 to promote their loading into multivesicular bodies. Together, these findings support a model in which m6A governs the partitioning of miRNAs between intracellular silencing and extracellular communication.