AGO1, encoding the Argonaute 1 protein, functions in gene-silencing pathways mediated by small non-coding RNAs. It is involved in various biological processes, such as plant growth and development, and is also crucial in mammalian cell development and metabolism [1,2]. In plants, it physically interacts with HSP90 to buffer genetic variation [2].

In mouse models, EC-AGO1 knockout (KO) leads to an anti-obesity phenotype, with lower body weight, improved insulin sensitivity, and enhanced adipose tissue browning and thermogenesis. Mechanistically, EC-AGO1 suppression inhibits thrombospondin-1 (THBS1), an anti-angiogenic and pro-inflammatory cytokine [3]. In myogenic differentiation, Ago1 is required for activation of the myogenic program by regulating enhancer RNA (eRNA)-CREB-binding protein (CBP) acetyltransferase interaction [4]. In mouse embryonic stem cells (mESCs), Ago1 depletion results in a specific redistribution of the repressive histone mark H3K9me3 and the heterochromatin protein HP1α away from pericentromeric regions, and up-regulation of major satellite transcripts [5].

In conclusion, AGO1 plays essential roles in gene-silencing pathways and is involved in diverse biological processes from plant development to mammalian cell differentiation, metabolism, and chromatin organization. Mouse KO models have revealed its significance in metabolic disorders and cell differentiation, providing insights into potential therapeutic targets for related diseases.