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Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.
Thiffault, Isabelle; Wolf, Nicole I; Forget, Diane; Guerrero, Kether; Tran, Luan T; Choquet, Karine; Lavallée-Adam, Mathieu; Poitras, Christian; Brais, Bernard; Yoon, Grace; Sztriha, Laszlo; Webster, Richard I; Timmann, Dagmar; van de Warrenburg, Bart P; Seeger, Jürgen; Zimmermann, Alíz; Máté, Adrienn; Goizet, Cyril; Fung, Eva; van der Knaap, Marjo S; Fribourg, Sébastien; Vanderver, Adeline; Simons, Cas; Taft, Ryan J; Yates, John R; Coulombe, Benoit; Bernard, Geneviève.
Afiliación
  • Thiffault I; 1] Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada. [2] Service de Génétique, Centre Hospitalier Universitaire Sai
  • Wolf NI; Department of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands.
  • Forget D; Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins ouest, Montréal, Québec H2W 1R7, Canada.
  • Guerrero K; Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.
  • Tran LT; Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.
  • Choquet K; Neurogenetics of Motion Laboratory, Montreal Neurological Institute, 3801 University Street, McGill University, Montreal, Quebec H3A 2B4, Canada.
  • Lavallée-Adam M; Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road SR302, La Jolla, California 92037, USA.
  • Poitras C; Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins ouest, Montréal, Québec H2W 1R7, Canada.
  • Brais B; Neurogenetics of Motion Laboratory, Montreal Neurological Institute, 3801 University Street, McGill University, Montreal, Quebec H3A 2B4, Canada.
  • Yoon G; Division of Neurology and Clinical and Metabolic Genetics, the Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
  • Sztriha L; Department of Paediatrics, Faculty of Medicine, University of Szeged, Temesvári krt. 35-37, Szeged H-6726, Hungary.
  • Webster RI; 1] T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia. [2] Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead New South Wales 2145, Australia
  • Timmann D; Department of Neurology, University Clinic Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany.
  • van de Warrenburg BP; Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, PO Box 9101, Nijmegen 6500 HB, The Netherlands.
  • Seeger J; Department of Pediatrics and Adolescent Medicine, Deutsche KlinikfürDiagnostik, Wiesbaden 65191, Germany.
  • Zimmermann A; Department of Paediatrics, Faculty of Medicine, University of Szeged, Temesvári krt. 35-37, Szeged H-6726, Hungary.
  • Máté A; Department of Neurosurgery, Faculty of Medicine, University of Szeged, 6 Semmelweis Street, Szeged H-6725, Hungary.
  • Goizet C; Service de Génétique, Hôpital Pellegrin, CHU Bordeaux and University Bordeaux, Laboratoire MRGM (EA4576), Bordeaux 33076, France.
  • Fung E; Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR China.
  • van der Knaap MS; Department of Child Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands.
  • Fribourg S; 1] Université de Bordeaux, Institut Européen de Chimie et Biologie, ARNA Laboratory, Pessac F-33607, France. [2] Institut National de la Santé Et de la Recherche Médicale, INSERM-U869, ARNA Laboratory, Bordeaux F-33000, France.
  • Vanderver A; 1] Center for Genetic Medicine Research, Children's National, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010, USA. [2] Department of Neurology, Children's National, 111 Michigan Avenue Northwest, Washington, District of Columbia 20010, USA. [3] George Washington University, Sc
  • Simons C; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
  • Taft RJ; 1] George Washington University, School of Medicine, Washington, District of Columbia 20052, USA. [2] Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia. [3] Departments of Integrative Systems Biology and Pediatrics, School of Medicine and Health Scien
  • Yates JR; Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road SR302, La Jolla, California 92037, USA.
  • Coulombe B; 1] Translational Proteomics Laboratory, Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins ouest, Montréal, Québec H2W 1R7, Canada. [2] Department of Biochemistry, Université de Montréal, Pavillon Roger-Gaudry, CP 6128, Succ Centre-Ville, Montreal, Québec H3C 3J7, Canada.
  • Bernard G; Department of Neurology and Neurosurgery, McGill University, Department of Medical Genetics, Montreal Children's Hospital, Research Institute of the McGill University Health Center, 1001 boul Décarie, Montreal, Quebec H4A 3J1, Canada.
Nat Commun ; 6: 7623, 2015 Jul 07.
Article en En | MEDLINE | ID: mdl-26151409
A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: ARN Polimerasa III / ARN Polimerasas Dirigidas por ADN / Predisposición Genética a la Enfermedad / Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias / Genes Recesivos Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: ARN Polimerasa III / ARN Polimerasas Dirigidas por ADN / Predisposición Genética a la Enfermedad / Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias / Genes Recesivos Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article