Biogenesis of microRNAs. MiRNAs are transcribed by RNA polymerase II (Pol II) to generate a long precursor transcript named primary microRNA (pri-miRNA). This RNA molecule folds up into a secondary structure (stem-loop) to form a partial double helix, composed of 100–1000 nt with a 5′-cap. MiRNA maturation process can be divided into three phases. In the first, known as cropping, pri-miRNA is converted into the precursor miRNA (pre-miRNA) via the cutting activity of the Drosha enzyme, a nuclear endoribonuclease III. Pre-miRNA has a hairpin structure (stem-loop) and a length of about 70–80 nt. Following cropping, the pre-miRNA has a 5′P and a 3′OH and 2–3 nt at the protruding end with a single strand. In the second phase, the nuclear export factors Exportin-5 and ras-related nuclear protein (RAN-GTP) mediate the export of pre-miRNAs from nucleus to cytoplasm. In the third phase, known as dicing, another type of RNA endonuclease III, known as Dicer, processes pre-miRNA in the cytoplasm by cleaving it into an 18–22 nt double-stranded miRNA (miRNA duplex). Lastly, mature miRNA incorporated into the RNA-induced silencing complex (RISC) is able to bind the 3′UTR region of its target mRNA.