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FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.
Zhang, Tao; Wu, Yen-Ching; Mullane, Patrick; Ji, Yon Ju; Liu, Honghe; He, Lu; Arora, Amit; Hwang, Ho-Yon; Alessi, Amelia F; Niaki, Amirhossein G; Periz, Goran; Guo, Lin; Wang, Hejia; Elkayam, Elad; Joshua-Tor, Leemor; Myong, Sua; Kim, John K; Shorter, James; Ong, Shao-En; Leung, Anthony K L; Wang, Jiou.
Afiliação
  • Zhang T; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Wu YC; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Mullane P; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Ji YJ; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Liu H; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • He L; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Arora A; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Hwang HY; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Alessi AF; Department of Biology, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Niaki AG; Department of Biophysics, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Periz G; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Guo L; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Wang H; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Elkayam E; Keck Structural Biology Laboratory, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
  • Joshua-Tor L; Keck Structural Biology Laboratory, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
  • Myong S; Department of Biophysics, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Kim JK; Department of Biology, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Shorter J; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Ong SE; Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
  • Leung AKL; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Wang J; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: jiouw@jhu.edu.
Mol Cell ; 69(5): 787-801.e8, 2018 03 01.
Article em En | MEDLINE | ID: mdl-29499134
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.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Caenorhabditis elegans / RNA de Helmintos / Inativação Gênica / Proteínas de Caenorhabditis elegans / Proteína FUS de Ligação a RNA / MicroRNAs Limite: Animals / Humans Idioma: En Revista: Mol Cell Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Caenorhabditis elegans / RNA de Helmintos / Inativação Gênica / Proteínas de Caenorhabditis elegans / Proteína FUS de Ligação a RNA / MicroRNAs Limite: Animals / Humans Idioma: En Revista: Mol Cell Ano de publicação: 2018 Tipo de documento: Article