Fig. 1

Biosynthesis, processing and effector action of miRNA. miRNA gene is transcribed by RNA polymerase II into a long transcript known as primary miRNA (pri-miRNA) which is further trimmed by microprocessor complex (Drosha and DGCR8) into an approximately 70 nucleotide- long hairpin structure known as pre-miRNA. Subsequently, Exportin-5 binds to the pre-miRNA and to a GTP-Ran, forming a heterotrimeric complex which passes through the nuclear membrane. After translocation to the cytoplasm, the GTPase activity of Ran catalyzes the hydrolysis of GTP into GDP to facilitate the release of pre-miRNA from exportin-5. Exportin-5 then returns to the nucleus and available for another round of pre-miRNA transport. Once released in the cytoplasm, a specialized multi-domain ribonuclease III enzyme known as Dicer further processes the pre-miRNAs to form a miRNA-miRNA duplex. One strand (anti-sense strand) of the resulting miRNA-miRNA duplex is loaded onto Argonaute proteins leading to the formation of miRNA-induced silencing complex (miRISC). Partial complementary base pairing occurs between the seed region (2 to 8 nucleotides from the 5′-proximal region) of the miRNA and the seed map site (complementary to the seed region) of the target mRNA. The ultimate effect may be either endo-nucleolytic cleavage or translational repression of the target mRNA