Biogenesis and mechanism of action of miRNAs. (a) miRNAs are transcribed mainly by polymerase II (A) from a gene encoding a single miRNA (B), or from a polycistronic gene (C), or from a gene in an intronic region (D). Resulting pri-miRNAs are processed by type III RNase Drosha. The newly formed stem-loop structure, pre-miRNA, is recognized by the XPO5, RanGTP complex, and is transported to the cytoplasm by exportin-5 (E). Dicer cleaves the loop (F), leaving a double-stranded fragment, the miRNA-3p:miRNA-5p duplex (G). The duplex is then unwound and loaded into the miRISC complex (H) where it recognizes and anneals to the UTR of mRNA target (I). The messenger RNA:miRISC complex mediates translational repression (J) or mRNA decay (K). (b) Processing of a pre-miRNA gives rise to two mature miRNAs named miR-XXX-3p and miR-XXX-5p where miR-XXX-3p miRNA originates from 3′-end and miR-XXX-5p miRNA originates from 5′-end of the pre-miRNA.