Fig. 1.

Biogenesis of miRNAs is a multistep process (Lee et al., 2003, 2004; Calin and Croce, 2006; Ha and Kim, 2014; Bartel, 2018). miRNA host genes are located in intragenic or intergenic regions and are primarily transcribed into a long, capped (Bartel, 2009), and polyadenylated transcript (pri-miRNAs) by RNA polymerase II, which is often longer than several kilobases (Lee et al., 2004). The pri-miRNAs are first processed in the nucleus into a shorter hairpin-structured transcript (pre-miRNAs) by the nuclear enzyme Drosha (Lee et al., 2003). The hairpin-loop pre-miRNAs are exported into the cytoplasm through a nuclear member channel protein, Exportin-5 (Yi et al., 2003). In the cytoplasm, pre-miRNAs are further processed by Dicer to a hairpin-free duplex form of miRNA called mature miRNAs (Hutvágner et al., 2001; Ketting et al., 2001). The duplex miRNAs bind with Argonaute 2 (Ago2) and transactivation-responsive RNA-binding protein (TRBP) to form RISC, and then a functional strand of the duplex miRNA remains in RISC until it binds to its target mRNA while the unfunctional strand is degraded. The eight-base-long seed sequences on the mature miRNA recognize and bind to their partial complementary sequences on the 3′ UTR of target gene mRNAs. The complex between miRNA and mRNA rapidly represses the translation of mRNA into proteins and eventually leads to mRNA degradation (Bartel, 2009, 2018; Eichhorn et al., 2014). DGCR8, Drosha and DiGeorge syndrome chromosome region; ORF, open reading frame.