MicroRNA Biogenesis

MicroRNAs (miRNA) are non-coding RNA molecules with 21-24 nucleotide length. Basically, miRNAs cause either inhibition of protein translation or degradation of mRNA. Although it was thought to be an unusual specific gene expression mechanism when first discovered, it is now accepted as a pivotal regulator of gene expression. Biogenesis of miRNA begins with RNA polymerase II in nucleus and turns out to be long hairpin that contains mature long miRNA sequence (pri-miRNA). Hairpin structure is cleaved by microprocessor complex composed of Drosha (RNAse III) and DiGeorge critical syndrome region 8 (DGCR8). Pre-miRNA is transported by Exportin 5 from nucleus to cytoplasm and in turn cleaved to 21-24 nucleotide long miRNA duplex by RNAse III (Dicer). The strand converted to mature sequence is loaded to Argonaute on RNA induced silencing complex (RISC). MicroRNAs has seed a sequence, 2-8 nucleotide in length. When the seed sequence binds to target mRNA with a perfect complementarity, it destabilizes the mRNA. However, when it binds to target mRNA with imperfect complementarity, causes the inhibition of translation. Although miRNAs play role in development, differentiation, and other physiological events, aberrant expression of miRNA is associated with different pathological conditions. The understanding of epigenetic effect of miRNA biogenesis on different physiological processes and diseases has potential importance at the molecular level.