Narasimhan Srinaath, Erkeland Stefan J
Department of Immunology, Erasmus Medical Centre, Dr. Molenwaterplein 40, 3015 GD Rotterdam, The Netherlands.
Noncoding RNA. 2025 Aug 19;11(4):62. doi: 10.3390/ncrna11040062.
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.
微小RNA（miRNA）是关键的转录后调节因子，可在包括发育、增殖和凋亡在内的多个细胞过程中控制基因表达。它们的生物合成涉及一个多步骤途径，包括初级转录本的加工以及以Argonaute（AGO）蛋白为核心的RNA诱导沉默复合体（RISC）的组装。本综述全面概述了装载miRNA的RISC（miRISC）的分子动力学，重点关注翻译后修饰、AGO的相互作用分子以及微调并协调miRISC活性的机制。miRISC的组成会影响AGO的稳定性、定位和沉默效率，从而维持细胞内稳态和发育，并介导对各种类型细胞应激的反应。我们将讨论一些不常见的调节机制，例如在缺氧或2型T细胞反应期间AGO的修饰以及miRISC与众多RNA结合蛋白（RBP）的功能。本综述旨在突出在理解miRISC驱动的基因沉默复杂调节方面的最新进展。
