Skip to main content
. 2020 Jul 19;16(14):2628–2647. doi: 10.7150/ijbs.47203

Figure 1.

Figure 1

Canonical miRNA biogenesis and miRNA-mediated gene silencing. Transcribed by RNA Pol II, one nuclear miRNA gene produces a pri-miRNA, which is then recognized and cleaved into pre-miRNA by a microprocessor basically consisting of Drosha and DGCR8. Next, the pre-miRNA is exported to the cytoplasm with the help of Exportin 5 and RanGTP, further recognized and cut by Dicer and TRBP, and generates the miRNA-miRNA* duplex. After loaded into an Ago protein, the miRNA* strand is commonly degraded, while the miRNA strand forms the functional RISC. Upon loaded into RISC, the mature miRNA guides RISC to complementary target sequences located generally in the 3' untranslated region (3'-UTR) of mRNAs, then can function with the mode of mRNA degradation or translational repression. In the mRNA degradation mode, by the interactions with Ago protein, the GW182 recruits PABPC and binds the cytoplasmic deadenylase complexes PAN2-PAN3 and CCR4-NOT, rapid 5′-3′ mRNA degradation can also be in progress with the participation of DCP1-DCP2 complex. In the translational repression mode, the interaction of GW182 and CCR4-NOT can recruit DDX6 (a known translational inhibitor), and the release of eIF4AI or eIF4AII can inhibit the translation initiation. RNA Pol II, RNA polymerase II; DGCR8, DiGeorge syndrome critical region gene 8; RanGTP, Ran guanosine triphosphate; TRBP, HIV-1 TAR RNA binding protein; Ago, Argonaute; RISC, RNA-induced silencing complex; PABPC, polyadenylatebinding protein; PAN2-PAN3, poly(A)-nuclease deadenylation complex subunit 2 (PAN2)-PAN3; CCR4-NOT, carbon catabolite repressor protein 4 (CCR4)-NOT; DCP1-DCP2, mRNA-decapping enzyme subunit 1 (DCP1)-DCP2; DDX6, DEAD-box protein 6; eIF4A, eukaryotic translation initiation factor 4 A.