Fig. (1) Schematic miRNA biogenesis and regulation. The miRNA gene is transcribed (pri-miRNA) and cut in the nucleus to generate pre-miRNA.
Pre-miRNA is transported to the cytoplasm and is further processed there. Mature miRNA is originated as a mature
miRNA:miRNA* (passenger strand) duplex. Mature miRNA is incorporated in RISC to bind a target mRNA. Perfect miRNA-mRNA
binding leads to mRNA cleavage, while imperfect miRNA-mRNA binding leads to translational repression (rarely to translational
stimulation). Levels of cellular bioactive miRNA can be controlled by both transcriptional regulation, including epigenetic modifications and
target-dependent loops, and post-transcriptional regulation, including decoy mechanisms exerted by pseudogenes, and intercellular exosomedependent
trafficking. DNMTs = DNA methyltransferases; HDACs = histone deacetylases; DGCR8 = DiGeorge syndrome critical region 8;
RISC = RNA-induced silencing complex; ψ = pseudogene.