Argonaute RISC catalytic component 2 (AGO2)

Argonaute RISC catalytic component 2 (AGO2) is a central, catalytically active enzyme of the Argonaute protein family in humans, with critical roles in the RNA interference (RNAi) pathway and microRNA-mediated gene silencing. AGO2 binds small RNAs (siRNAs, miRNAs) and, as the main catalytic “slicer” among mammalian Argonautes, it cleaves target mRNAs with high sequence complementarity. Beyond its cytoplasmic role, AGO2 is involved in chromatin modulation, transcriptional repression, and alternative splicing in the nucleus. Its activity is essential for normal development, stem cell function, and the control of gene expression, and its dysfunction is implicated in cancer and other diseases[1][3][4]. AGO2 is the only human Argonaute protein with robust endonuclease activity required for siRNA-mediated target mRNA cleavage, and its regulation involves complex structural domains (PAZ, MID, and PIWI) and post-translational modifications. AGO2 activity constitutes a core mechanism of post-transcriptional gene regulation and epigenetic control in eukaryotic cells[3][4].

Other names

Argonaute-2Protein argonaute-2EIF2C2hAgo2eIF-2C 2PPDQ10PAZ Piwi domain proteinProtein slicerArgonaute 2RISC catalytic componentEukaryotic translation initiation factor 2C 2Cancer susceptibility candidate 7 (non-protein coding)LINC00980 (occasionally co-annotated or related, but not a canonical protein synonym)

Not applicable for direct drugs. Mechanistically, molecules targeting AGO2 or its associated processes may: Enhance or inhibit AGO2/siRNA or AGO2/miRNA complex formation; Block or mimic guide RNA binding; Interfere with RISC assembly or mRNA cleavage; Modulate AGO2 post-translational modifications to alter gene silencing efficacy[3].