Fig. 1

The mechanism of exosomal miRNAs loading. In the nucleus, Pol-II enzyme transcribes primary miRNAs (pri-miRNA) from miRNA-related genes. DGCR8 and Drosha structure catalyzes pri-RNAs into pre-miRNAs form, which is transferred toward cytoplasm employing exportin-5 protein. At the cytoplasmic level, the pre-miRNAs are trimmed into double-stranded miRNAs through the Dicer complex action. Then Helices, a splicing enzyme, generates mature miRNAs which harbors single-stranded. In the final step, MVBs (exosomes) capture mature miRNAs via four possible mechanisms including: 3′ miRNA sequence-dependent pathway, nSMase2-dependent pathway, the miRNAISC-based pathway, and sumoylated hnRNPs-related pathway. Other biological materials are sorted into exosomes through endocytosis, Golgi apparatus, different protein complexes, and ESCRT machinery randomly or/and preferentially. Of note, after exosome maturation, MVB could back fuse with the PM in which decorate the mother cell PM with specific receptors (I). Another fate is that MVB combine to the PM and exports its cargoes to the ECM (pathway II). Scientists believe that MVB may select degradation pathway where it combine with lysosomes (pathway III) and its content is degraded. Different proteins such as Rab-GTPase and SNAREs contribute in intracellular MVB trafficking and fusion. Three possible mechanisms were proposed by which exosomes can alter target cell function, I: endocytotic pathway; II: ligand-receptor interaction; III: direct fusion