Abstract
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. Zhang et al. find that the RNA-binding protein FUS is required for miRNA-mediated gene silencing. FUS interacts with Argonaute, microRNAs, and target transcripts, promoting interactions that lead to gene silencing.
Original language | English (US) |
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Pages (from-to) | 787-801.e8 |
Journal | Molecular cell |
Volume | 69 |
Issue number | 5 |
DOIs | |
State | Published - Mar 1 2018 |
Keywords
- AGO2
- ALS
- Argonaute
- C. elegans
- FTD
- FUS
- RNA
- gene silencing
- microRNA
- neurodegeneration
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology