First Author | Zhang T | Year | 2018 |
Journal | Mol Cell | Volume | 69 |
Issue | 5 | Pages | 787-801.e8 |
PubMed ID | 29499134 | Mgi Jnum | J:260809 |
Mgi Id | MGI:6150122 | Doi | 10.1016/j.molcel.2018.02.001 |
Citation | Zhang T, et al. (2018) FUS Regulates Activity of MicroRNA-Mediated Gene Silencing. Mol Cell 69(5):787-801.e8 |
abstractText | 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. |