Figure 1.

A schematic illustration of microRNA biogenesis and extracellular vesicle microRNA transfer. In the nucleus of the donor cells, miRNA genes are transcribed by RNA polymerase II (Pol II), forming a primary transcript (pri-miRNA). This is then processed by the RNase III-type endonuclease family protein Drosha into a precursor molecule (pre-miRNA). It is then exported to the cytoplasm by the transport protein exportin-5. In the cytoplasm, pre-miRNA is further processed by another RNase III-type endonuclease family protein, Dicer, which generates an intermediary miRNA duplex, of which one strand is loaded onto the RNA-induced silencing complex (RISC) to form mature miRNA. On the one hand, these mature miRNA can be directly transferred to the recipient cells by microvesicles, which are shed from the plasma membrane. On the other hand, these mature miRNA and some pre-miRNA can be loaded into the multivesicular bodies (MVBs), which are generated via early-endosomal membrane invagination. These MVBs then dock onto the cell membrane and release positive exosomes into the extracellular space (including serum and other biological fluids). The exosomal fusion with the plasma membrane of the recipient cell, or phagocytosis followed by membrane fusion, leads to the release of miRNA cargo into the cytosol and translational repression.