Zhang, T., Wu, Y. C., Mullane, P., Ji, Y. J., Liu, H., He, L., Arora, A., Hwang, H. Y., Alessi, A. F., Niaki, A. G., Periz, G., Guo, L., Wang, H., Elkayam, E., Joshua-Tor, L., Myong, S., Kim, J. K., Shorter, J., Ong, S. E., Leung, A. K. L., Wang, J. (March 2018) FUS Regulates Activity of MicroRNA-Mediated Gene Silencing. Mol Cell, 69 (5). 787-801.e8. ISSN 1097-2765 (Public Dataset)
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Ago2 Als Argonaute C. elegans Ftd Fus Rna gene silencing microRNA neurodegeneration |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL labs > Joshua-Tor lab CSHL Cancer Center Program > Gene Regulation and Inheritance Program |
| Depositing User: | Matt Covey |
| Date: | 1 March 2018 |
| Date Deposited: | 07 Mar 2018 15:42 |
| Last Modified: | 05 Nov 2020 22:35 |
| PMCID: | PMC5836505 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/36205 |
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