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Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development.
Thomas-Jinu, Swapna; Gordon, Patricia M; Fielding, Triona; Taylor, Richard; Smith, Bradley N; Snowden, Victoria; Blanc, Eric; Vance, Caroline; Topp, Simon; Wong, Chun-Hao; Bielen, Holger; Williams, Kelly L; McCann, Emily P; Nicholson, Garth A; Pan-Vazquez, Alejandro; Fox, Archa H; Bond, Charles S; Talbot, William S; Blair, Ian P; Shaw, Christopher E; Houart, Corinne.
Afiliação
  • Thomas-Jinu S; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Gordon PM; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Fielding T; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Taylor R; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Smith BN; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.
  • Snowden V; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Blanc E; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Vance C; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.
  • Topp S; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.
  • Wong CH; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.
  • Bielen H; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Williams KL; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
  • McCann EP; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
  • Nicholson GA; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia; ANZAC Research Institute, University of Sydney, Concord Hospital, Sydney, NSW 2139, Australia.
  • Pan-Vazquez A; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK.
  • Fox AH; School of Anatomy, Physiology, and Human Biology, University of Western Australia, Crawley, WA 6009, Australia; Harry Perkins Institute for Medical Research, QEII Medical Centre, Nedlands, WA 6009, Australia; Centre for Medical Research, University of Western Australia, Crawley, WA 6009, Australia.
  • Bond CS; School of Chemistry and Biochemistry, University of Western Australia, Crawley, WA 6009, Australia.
  • Talbot WS; Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Blair IP; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
  • Shaw CE; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London SE5 8AF, UK.
  • Houart C; Centre for Developmental Neurobiology and MRC CNDD, IoPPN, Guy's Campus, King's College London, London SE1 1UL, UK. Electronic address: corinne.houart@kcl.ac.uk.
Neuron ; 94(2): 322-336.e5, 2017 Apr 19.
Article em En | MEDLINE | ID: mdl-28392072
ABSTRACT
Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons. Novel variants affecting the conserved coiled-coil domain, so far exclusively found in fALS exomes, specifically affect the ability of SFPQ to localize in axons. They broadly rescue morphology and motility in the zebrafish mutant, but alter motor axon morphology, demonstrating functional requirement for axonal SFPQ. Altogether, we uncover the axonal function of the splicing factor SFPQ in motor development and highlight the importance of the coiled-coil domain in this process. VIDEO ABSTRACT.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Axônios / Splicing de RNA / Fator de Processamento Associado a PTB / Neurônios Motores Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Axônios / Splicing de RNA / Fator de Processamento Associado a PTB / Neurônios Motores Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article