Ionizing Radiation Actively Reshapes Bone Marrow-Derived Extracellular Vesicle MicroRNA Cargo with the Involvement of hnRNP A2b1

Bone marrow (BM) is highly sensitive to ionizing radiation: high doses cause extensive cell death, BM failure, and immune suppression, whereas low doses may increase long-term cancer risk without acute toxicity. Radiation-induced BM effects are partly mediated by disrupted intercellular communication via extracellular vesicles (EVs), including alterations in their microRNA cargo. EV–microRNA packaging remains unclear, although RNA-binding proteins are thought to contribute. To address this, murine BM cells and EVs were isolated 24 h after total body irradiation (0, 0.1, or 3 Gy). MicroRNAs were analyzed using nCounter and validated by RT–qPCR, while RNA-binding proteins (hnRNP A2b1, hnRNP Q) were assessed by Western blotting and confocal microscopy. Protein–microRNA interactions were examined using motif analysis and immunoprecipitation, and functional associations were explored via KEGG pathway analysis. High-dose irradiation induced widespread microRNA changes, whereas low-dose irradiation had minimal effects. Distinct cellular and EV microRNA profiles indicated selective sorting, with specific microRNAs enriched in cells but depleted in EVs. hnRNP A2b1 emerged as a potential regulator, showing nuclear relocalization and reduced EV association after irradiation; these changes correlated with decreased export of motif-containing microRNAs, possibly linked to key BM pathways. Overall, radiation alters EV–microRNAs through dose-dependent, protein-mediated selective sorting, potentially affecting BM communication and homeostasis.