Journal
MOLECULAR CELL
Volume 69, Issue 5, Pages 787-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2018.02.001
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Funding
- NIH [NS074324, NS089616, T32CA009110, GM104135, GM088565]
- Packard Center for ALS Research at Johns Hopkins
- ALS Association
- Muscular Dystrophy Association
- DOD [BC101881]
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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 micro-RNA-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.
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