Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells

Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study, a team led by researchers from Yale University School of Medicine describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. They have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

Suppression mediated by dsRNA is not TLR3-dependent and can be blocked by anti-miR to miR-150.