Module 4: Figure microRNA biogenesis
Biogenesis and function of microRNA.
RNA polymerase II (Pol II) transcribes miRNA genes to form primary miRNA (pri-miRNA) transcripts, which has a characteristic stem-cell structure. The latter is recognized by the ribonuclease Drosha that acts together with DiGeorge syndrome critical region 8 (DGCR8, also known as Pasha) to cleave pri-miRNA to form pre-miRNA, which is then exported from the nucleus by Exportin 5. Once it enters the cytoplasm, the pre-miRNA is recognized by TAR RNA-binding protein (TRBP) and the ribonuclease called Dicer, which cleaves the precursor to form the mature microRNA (miR). The miR acts by binding to Argonaute (Ago1–4) proteins to form a RNA-silencing complex (RISC) that recognizes and inhibits target messenger RNAs (mRNAs) through a number of mechanisms, such as translational repression, mRNA deadenylation and mRNA degradation.