Protein Argonaute-2 (AGO2) (AGO2)

Protein Argonaute-2 (AGO2) is the central catalytic component of the RNA-induced silencing complex (RISC) and is essential for RNA interference (RNAi) in mammals. It possesses endoribonuclease activity, often referred to as "Slicer" activity, which allows it to cleave messenger RNA (mRNA) molecules that are perfectly complementary to the guide RNA (siRNA or miRNA) it carries (UniProt: Q9UKV8). Beyond cleavage, AGO2 also mediates gene silencing through translational repression and mRNA destabilization when complementarity is imperfect (PubMed: 15284453). In the context of human disease, AGO2 is frequently dysregulated in various cancers, where it can promote tumor progression by modulating the expression of oncogenes or tumor suppressors (PubMed: 25237114). As a therapeutic target, AGO2 is the primary effector for all approved siRNA-based drugs, which leverage the protein's natural mechanism to achieve highly specific knockdown of disease-associated genes (PubMed: 32034750). Ongoing research also explores small molecule inhibitors of AGO2 to disrupt its role in oncogenic miRNA processing and viral replication.

Other names

EIF2C2Eukaryotic translation initiation factor 2C 2hAgo2Argonaute2PAZ Piwi domain proteinSlicer

AGO2 acts as the catalytic component of the RNA-induced silencing complex (RISC), binding small interfering RNAs (siRNAs) or microRNAs (miRNAs) to guide the sequence-specific cleavage or translational repression of target messenger RNA (mRNA).