Figure 2

miRNA biogenesis and release mechanism to recipient cells. miRNA genes are transcribed in the nucleus in pre-miRNAs and exported into cytoplasm. The DICER complex by cleavage generates an intermediary miRNA duplex, of which one strand is incorporated into RNA-induced silencing complex (RISC) to form mature miRNA. A fraction of miRNAs are released from cells into the extracellular environment (i) within multi-vesicular bodies (MVB) and secreted via exosomes; (ii) incorporated into high-density lipoproteins (HDL) particles; (iii) associated with RNA-binding proteins, such as AGO2 and released of the miRNA–AGO complex. Exosome miRNAs (exo-miRs) are involved in cell-to-cell communication. Exo-miRs are released into the extracellular compartment acting as autocrine/paracrine mechanism, or in the blood stream with endocrine effect. Exosome containing miRNAs are uptaken and internalized into cytoplasm of recipient cells through endocytosis pathway. The exosome uptake mechanisms involve protein interactions that facilitate subsequent endocytosis.