FUS 调节 miRNA 介导的基因沉默活性。
FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.
机构信息
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Biology, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
出版信息
Mol Cell. 2018 Mar 1;69(5):787-801.e8. doi: 10.1016/j.molcel.2018.02.001.
MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression. It remains unclear how the efficiency of RNA silencing could be influenced by RNA-binding proteins associated with the microRNA-induced silencing complex (miRISC). Here we report that fused in sarcoma (FUS), an RNA-binding protein linked to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), interacts with the core miRISC component AGO2 and is required for optimal microRNA-mediated gene silencing. FUS promotes gene silencing by binding to microRNA and mRNA targets, as illustrated by its action on miR-200c and its target ZEB1. A truncated mutant form of FUS that leads its carriers to an aggressive form of ALS, R495X, impairs microRNA-mediated gene silencing. The C. elegans homolog fust-1 also shares a conserved role in regulating the microRNA pathway. Collectively, our results suggest a role for FUS in regulating the activity of microRNA-mediated silencing.
MicroRNA 介导的基因沉默是基因表达调控的基本机制。目前尚不清楚与 microRNA 诱导的沉默复合物（miRISC）相关的 RNA 结合蛋白如何影响 RNA 沉默的效率。在这里，我们报告说，融合肉瘤蛋白（FUS）是一种与包括肌萎缩侧索硬化症（ALS）在内的神经退行性疾病相关的 RNA 结合蛋白，它与 miRISC 的核心成分 AGO2 相互作用，是优化 microRNA 介导的基因沉默所必需的。FUS 通过与 microRNA 和 mRNA 靶标结合来促进基因沉默，这可以从其对 miR-200c 和靶标 ZEB1 的作用中得到证明。导致携带者患有侵袭性肌萎缩侧索硬化症的 FUS 截短突变体形式 R495X 会损害 microRNA 介导的基因沉默。秀丽隐杆线虫的同源物 fust-1 也在调节 microRNA 途径方面具有保守作用。总的来说，我们的结果表明 FUS 在调节 microRNA 介导的沉默活性中发挥作用。
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