Figure 1.
MicroRNA biogenesis and the mechanism of microRNA-mediated gene silencing. MicroRNAs (miRNAs) are short, double-stranded RNA molecules of approximately 19–23 nt in length. The primary transcripts of miRNAs (pri-miRNAs) are transcribed by RNA polymerase II from varied genomic loci. Primary miRNA transcripts are processed into precursor miRNA (pre-miRNA) stem-loops of approximately 60 nt in length by the nuclear RNase III enzyme, Drosha, which is assisted by DiGeorge syndrome critical region gene 8 (DGCR8). These pre-miRNAs are then exported into the cytoplasm by a Ran-GTP-dependent nuclear transport receptor, exportin 5, where they are further processed into approximately 22-nt miRNA duplexes by the type III RNase, Dicer. The final step of miRNA maturation is the selective loading of the functional strand of the small RNA duplex into the RNA-induced silencing complex (RISC). Mature miRNAs then guide the complex to their complementary mRNAs for regulation of gene expression. Regulation is be mediated by various mechanisms including repression of translation, mRNA cleavage and deadenylation. Ran-GTP, ras-related nuclear protein-guanosine triphosphate.