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Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.
Martinez, Fernando J; Pratt, Gabriel A; Van Nostrand, Eric L; Batra, Ranjan; Huelga, Stephanie C; Kapeli, Katannya; Freese, Peter; Chun, Seung J; Ling, Karen; Gelboin-Burkhart, Chelsea; Fijany, Layla; Wang, Harrison C; Nussbacher, Julia K; Broski, Sara M; Kim, Hong Joo; Lardelli, Rea; Sundararaman, Balaji; Donohue, John P; Javaherian, Ashkan; Lykke-Andersen, Jens; Finkbeiner, Steven; Bennett, C Frank; Ares, Manuel; Burge, Christopher B; Taylor, J Paul; Rigo, Frank; Yeo, Gene W.
Afiliação
  • Martinez FJ; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Pratt GA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioinformatics and Systems Biology, University of California,
  • Van Nostrand EL; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Batra R; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Huelga SC; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Kapeli K; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Physiology, Yong Loo Lin School of Medicine, National Univers
  • Freese P; Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Chun SJ; Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
  • Ling K; Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
  • Gelboin-Burkhart C; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Fijany L; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Wang HC; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Nussbacher JK; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Broski SM; Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
  • Kim HJ; Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Lardelli R; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Sundararaman B; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Donohue JP; Department of Molecular, Cell, and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Javaherian A; Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
  • Lykke-Andersen J; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Finkbeiner S; Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Departments of Neurology and Physiology, University of California, San Francisco, San Francisco, CA 94107, USA.
  • Bennett CF; Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
  • Ares M; Department of Molecular, Cell, and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Burge CB; Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Taylor JP; Howard Hughes Medical Institute, Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Rigo F; Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.
  • Yeo GW; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioinformatics and Systems Biology, University of California,
Neuron ; 92(4): 780-795, 2016 Nov 23.
Article em En | MEDLINE | ID: mdl-27773581
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs) demonstrate abnormal splicing changes, likely due to increased nuclear-insoluble hnRNP A2/B1. Mutant iPSC-MNs display decreased survival in long-term culture and exhibit hnRNP A2/B1 localization to cytoplasmic granules as well as exacerbated changes in gene expression and splicing upon cellular stress. Our findings provide a cellular resource and reveal RNA networks relevant to neurodegeneration, regulated by normal and mutant hnRNP A2/B1. VIDEO ABSTRACT.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sobrevivência Celular / Processamento Alternativo / Transporte Proteico / Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B / Fibroblastos / Esclerose Lateral Amiotrófica / Neurônios Motores Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sobrevivência Celular / Processamento Alternativo / Transporte Proteico / Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B / Fibroblastos / Esclerose Lateral Amiotrófica / Neurônios Motores Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article