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CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome.
Asamitsu, Sefan; Yabuki, Yasushi; Ikenoshita, Susumu; Kawakubo, Kosuke; Kawasaki, Moe; Usuki, Shingo; Nakayama, Yuji; Adachi, Kaori; Kugoh, Hiroyuki; Ishii, Kazuhiro; Matsuura, Tohru; Nanba, Eiji; Sugiyama, Hiroshi; Fukunaga, Kohji; Shioda, Norifumi.
Afiliación
  • Asamitsu S; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
  • Yabuki Y; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
  • Ikenoshita S; Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Kawakubo K; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
  • Kawasaki M; Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
  • Usuki S; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
  • Nakayama Y; Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Adachi K; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
  • Kugoh H; Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • Ishii K; Liaison Laboratory Research Promotion Center, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan.
  • Matsuura T; Division of Radioisotope Science, Research Initiative Center, Organization for Research Initiative and Promotion, Tottori University, Tottori, Japan.
  • Nanba E; Division of Genomic Science, Research Initiative Center, Organization for Research Initiative and Promotion, Tottori University, Tottori, Japan.
  • Sugiyama H; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Tottori, Japan.
  • Fukunaga K; Chromosome Engineering Research Center, Tottori University, Tottori, Japan.
  • Shioda N; Department of the Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Sci Adv ; 7(3)2021 01.
Article en En | MEDLINE | ID: mdl-33523882
Fragile X-related tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease caused by CGG triplet repeat expansions in FMR1, which elicit repeat-associated non-AUG (RAN) translation and produce the toxic protein FMRpolyG. We show that FMRpolyG interacts with pathogenic CGG repeat-derived RNA G-quadruplexes (CGG-G4RNA), propagates cell to cell, and induces neuronal dysfunction. The FMRpolyG polyglycine domain has a prion-like property, preferentially binding to CGG-G4RNA. Treatment with 5-aminolevulinic acid, which is metabolized to protoporphyrin IX, inhibited RAN translation of FMRpolyG and CGG-G4RNA-induced FMRpolyG aggregation, ameliorating aberrant synaptic plasticity and behavior in FXTAS model mice. Thus, we present a novel therapeutic strategy to target G4RNA prionoids.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / G-Cuádruplex / Síndrome del Cromosoma X Frágil Límite: Animals Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Neurodegenerativas / G-Cuádruplex / Síndrome del Cromosoma X Frágil Límite: Animals Idioma: En Revista: Sci Adv Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos