Figure 1

miRNA biogenesis pathway and function: miRNAs are transcribed in the nucleus either from introns or exons of protein-coding genes or introns of long non-coding RNAs into primary transcripts (pri-miRNAs). Pri-miRNAs are then processed in two steps in the nucleus and cytoplasm, catalyzed by the RNase III type endonucleases Drosha and Dicer, in complexes with dsRNA-binding domain proteins, DGCR8 and TRBP respectively. In the canonical pathway, Drosha-DGCR8 processes the transcript to a stem loop-hairpin precursor (pre-miRNA). Intron derived miRNAs, called miRtrons, evade canonical pathway and processed by the spliceosome and the debranching enzyme into pre-miRNAs. Both canonical miRNAs and miRtrons are exported to the cytoplasm via Exportin 5, where they are further processed by Dicer-TRBP or by Ago2 to yield 20-25-bp miRNA duplexes. Dicer processing adds 5′ phosphate groups and two-nucleotide overhangs at the 3′ ends of the mature strands. The duplex produced by either Dicer or Ago2 is loaded onto an Argonaute protein of RISC where one strand is selected to function as mature miRNA while the partner miRNA* strand is preferentially degraded. The mature miRNA produced by these two mechanisms leads to translational repression or mRNA degradation.