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Updated: Sep 10, 2025

Protein Extract Preparation and Co-immunoprecipitation from Caenorhabditis elegans
Published on: May 23, 2020
Partners in Silencing: Decoding the Mammalian Argonaute Interactome
Srinaath Narasimhan1, Stefan J Erkeland1
1Department of Immunology, Erasmus Medical Centre, Dr. Molenwaterplein 40, 3015 GD Rotterdam, The Netherlands.
Abstract:
MicroRNAs (miRNAs) are key post-transcriptional regulators controlling gene expression across several cellular processes, including development, proliferation, and apoptosis. Their biogenesis involves a multi-step pathway, including the processing of primary transcripts and the assembly of the RNA-Induced Silencing Complex (RISC) with Argonaute (AGO) proteins at its core. This review provides a comprehensive overview of the molecular dynamics of miRNA-loaded RISC (miRISC), focusing on the post-translational modifications, the interactors of AGOs and the mechanisms that fine-tune and coordinate miRISC activity. The composition of miRISC influences AGO stability, localization, and silencing efficiency, thereby maintaining cellular homeostasis and development and mediating the response to various types of cellular stress. Uncommon regulatory mechanisms, including AGO modifications during, e.g., hypoxia or Type 2 T cell responses and miRISC functionality, with myriad RNA-binding proteins (RBPs), will be discussed. This review aims at highlighting the recent advances in the understanding of the intricate regulation of miRISC-driven gene silencing.
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