AGO2/Argonaute-2 Protein, Mouse (sf9, His)

The AGO2/Argonaute-2 protein is crucial for RNA-mediated gene silencing facilitated by the RNA-induced silencing complex (RISC). The 'minimal RISC' comprises AGO2 bound to a short guide RNA, such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs guide RISC to complementary mRNAs, initiating RISC-mediated gene silencing. The mechanism of gene silencing depends on the complementarity between the miRNA or siRNA and its target. Perfect complementarity leads to mRNA cleavage by AGO2, while partial complementarity results in translational inhibition, independent of endonuclease activity. AGO2 may inhibit translation initiation by binding to the 7-methylguanosine cap, preventing eIF4-E recruitment. It can also interact with EIF6, hindering the association of the 60S ribosomal subunit with the 40S subunit, leading to translational inhibition and mRNA accumulation in processing bodies. RISC-mediated translational repression is observed even for miRNAs with perfect 3'-UTR matches. Additionally, AGO2 plays a role in up-regulating translation under specific growth conditions, binding to the AU element in the 3'-UTR of TNF mRNA to enhance translation during serum starvation. Beyond its role in RNA silencing, AGO2 is essential for transcriptional gene silencing (TGS) where antigene RNAs or agRNAs direct the repression of complementary promoter regions. AGO2 regulates lymphoid and erythroid development and function independently of its endonuclease activity.