Fig. 1

miRNAs are encoded by genes located either independently (intergenic) or within introns of protein-coding genes (intronic). miRNA genes are transcribed by RNA polymerase II into primary miRNA (pri-miRNA), usually with 5′ cap and 3′ poly A structures. RNase III enzyme Drosha, together with its partner DGCR8 protein, cleaves pri-miRNAs to produce the 60–70 nt long hairpin precursors (pre-miRNA) through canonical pathway. Pri-miRNAs from intronic miRNA genes are also called miRtrons. miRtrons can be spliced to lariat structures by spliceosome and further processed to pre-miRNAs. The pre-miRNAs in nuclei are exported into the cytoplasm by exportin-5 protein and cleaved to short miRNA duplexes by RNase III enzyme Dicer. One strand (passenger strand or miRNA*) is expulsed and the other strand (guide strand, i.e., mature miRNA) is bound to Ago2 in RNA-induced silencing complex (RISC). Mature miRNA, primarily through the “seed” region (miRNA nucleotides 2–8), binds to specific sequences within target RNAs, typically within the 3′ untranslated region (UTR) of the protein coding RNAs or other transcripts to inhibit the expression of the targets to which they bind