Fig. 1.

The canonical pathway of miRNA biogenesis. a In the nucleus, the miRNA gene is transcribed by RNA polymerase II and then fold into a long pri-miRNA with a hairpin structure. The long pri-miRNA is then cleaved by the microprocessor complex made up of Drosha and DGCR8 (Pasha) proteins, generating a precursor miRNA (pre-miRNA). b Exportin-5 binds to the pre-miRNA and facilitates its export to the cytoplasm. In the cytoplasm, the type III RNase Dicer complex with the double-stranded RNA binding protein TRBP and PACT cleaves the precursor’s hairpin and the resulting duplex is isolated by a helicase enzyme. Finally, the functional strand is loaded together with the Argonaute (AGO) protein into the RNA-induced silencing complex (RISC) to target mRNAs by sequence complementary binding and mediates gene suppression through mechanisms of either translational repression or mRNA degradation