Fig 2

Biogenesis of miRNA. Starts in the nucleus when miRNA genes are transcribed by RNA polymerase II as large polyadenylated RNA molecules named primary miRNAs (pri-miRNAs). Pri-miRNAs are processed in the nucleus by RNase III Drosha and microprocessor complex subunit DGCR8. As a result, pri-miRNAs are cleaved into smaller double-stranded RNA (dsRNA) molecules known as pre-miRNAs and then are exported to the cytoplasm by exportin 5 (XPO5). Pre-miRNAs in the cytoplasm are cleaved and despoiled of their loops by the RNase III enzyme Dicer in association with TRBP into mature miRNAs consisting of a ∼22-nucleotide duplex. The last processing step is carried out by a ribonucleoprotein complex known as RNA-induced silencing complex (RISC), which can unwind both strands. Although either strand of the miRNA duplex could potentially act as a mature miRNA, usually only one of the strands is incorporated into the RISC complex to induce mRNA silencing. RISC-loading complex (RLC), consisted of Dicermm, Argonaute 2 (Ago2), and TRBP. Once loaded, the RISC complex finds a complementary strand, activates RNase and cleaves the RNA