Fig. 1.

miRNA biogenesis and loading into exosomes. miRNA genes are transcribed by RNA polymerase II (Pol II), forming pri-miRNAs in the nucleus. The Drosha complex cleaves pri-RNA to pre-miRNA, which is exported to the cytoplasm via exportin 5. Further cleavage by the Dicer complex generates an intermediary miRNA duplex, of which one strand is incorporated into the RNA-induced silencing complex (RISC) to form mature miRNA, which targets complementary mRNA for translational repression. Inward budding of the early and late endosome forms exosomes. During this process, mature miRNA, some pre-miRNAs and other RNA molecules, proteins, and lipids are loaded into the exosomes. Within exosomes, loaded pre-miRNAs may be processed into mature miRNA. The exosome-loading process involves an endosomal-sorting complex required for transport (ESCRT) or ceramide-dependent mechanisms. The fusion of multivesicular bodies (MVBs) with the plasma membrane releases exosomes. This process is dependent on Rab GTPases (e.g. Rab27). 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.