Protein Argonaute-2 (AGO2) and RNA-induced silencing complex (RISC) (AGO2/RISC)

Protein Argonaute-2 (AGO2) is the central catalytic component of the RNA-induced silencing complex (RISC), playing a pivotal role in the RNA interference (RNAi) pathway [1]. It functions as an endoribonuclease that binds small RNAs, such as microRNAs (miRNAs) or small interfering RNAs (siRNAs), which serve as guides to target complementary messenger RNA (mRNA) molecules for degradation or translational inhibition [1, 2]. In clinical medicine, AGO2 is the essential machinery utilized by siRNA-based therapeutics, such as Patisiran and Inclisiran, to achieve highly specific knockdown of disease-causing proteins [3, 4]. Dysregulation of AGO2 expression or RISC assembly is frequently observed in various cancers, where it can influence the processing of oncogenic or tumor-suppressive miRNAs, making it a potential target for direct inhibition [5]. Furthermore, AGO2 is involved in host-pathogen interactions, particularly in the defense against viral infections and the regulation of viral gene expression [6]. The therapeutic potential of AGO2 lies both in its role as an effector for RNAi drugs and as a target for modulating miRNA-mediated pathways in complex diseases. Sources: [1] UniProt (Q9UKV8); [2] Meister et al. (2004) Science; [3] Setten et al. (2019) Nat Rev Drug Discov; [4] FDA Drug Approvals; [5] Ye et al. (2015) J Cancer; [6] Swarts et al. (2014) Nat Struct Mol Biol.

Other names

EIF2C2Eukaryotic translation initiation factor 2C 2Argonaute 2hAgo2SlicerRISC

AGO2 acts as the catalytic engine of the RISC; it binds a single-stranded guide RNA (derived from siRNA or miRNA) and uses it to recognize complementary mRNA through Watson-Crick base pairing, leading to mRNA cleavage (slicing) or translational repression.