FUS Regulates Activity of MicroRNA-Mediated Gene Silencing

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)

URL: https://www.ncbi.nlm.nih.gov/pubmed/29499134
DOI: 10.1016/j.molcel.2018.02.001

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 labs > Joshua-Tor lab
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: Matt Covey
Date: 1 March 2018
Date Deposited: 07 Mar 2018 15:42
Last Modified: 07 Jan 2019 15:27
PMCID: PMC5836505
Related URLs:
Dataset ID:
URI: http://repository.cshl.edu/id/eprint/36205

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