Figure 2.
Biogenesis and actions of microRNAs. MicroRNAs (miRNAs) are initially transcribed in the nucleus as pri-miRNAs, which are processed into pre-miRNAs by the Drosha enzyme. Pre-miRNAs are further cleaved by Dicer to result in double-stranded miRNA duplexes. Drosha processing can be regulated by p53 or Smads (activated by TGF-β or BMPs). This process can also be inhibited via interactions of phosphorylated MeCP2 (by HIPK2) with DGCR8, a cofactor of Drosha. In addition, Dicer processing can be inhibited by MCPIP1, which is induced by MCP-1 (related to inflammation). Processing of let-7 family members is inhibited by Lin28b, which can be induced by TGF-β/Smad signaling. The miRNA duplexes are then unwound by the action of Dicer, and the mature miRNA guide strand is loaded into the RISC complex. Please refer to the main text for details. RISC, RNA-induced silencing complex; UTR, untranslated region. Modified from Kato et al.16