Argonaute 2 (AGO2) (AGO2)

Argonaute 2 (AGO2) is the essential catalytic engine of the RNA-induced silencing complex (RISC) and the RISC-loading complex (RLC), serving as the primary mediator of RNA interference (RNAi) in humans (UniProt P98170). It functions as an RNA-guided endonuclease that utilizes small interfering RNAs (siRNAs) or microRNAs (miRNAs) to identify and cleave complementary messenger RNA (mRNA) transcripts, leading to post-transcriptional gene silencing (PubMed 15284275). AGO2 is uniquely characterized among the human Argonaute family by its slicer activity, which is facilitated by its PIWI domain (PubMed 15284274). In clinical medicine, AGO2 is the functional target for a growing class of siRNA-based therapeutics, such as Patisiran and Inclisiran, which harness the protein's endogenous mechanism to degrade specific disease-associated mRNAs (DrugBank DB14582). Dysregulation of AGO2 is linked to various pathologies, including oncogenesis, where it can promote cell proliferation, and rare neurodevelopmental disorders like Lessel-Kreienkamp syndrome (Nature Communications 11, 5797). Beyond its role in gene regulation, AGO2 is involved in various physiological processes, including development and cellular differentiation (NCBI Gene 27161). While most current therapies utilize AGO2 as a tool, research is also exploring small molecule inhibitors of AGO2 for specific oncogenic or viral applications.

Other names

Eukaryotic translation initiation factor 2C 2EIF2C2Protein slicerhAgo2Argonaute RISC catalytic component 2RISC loading complex subunit AGO2

RNA-guided endonucleolytic cleavage of target mRNA