51. Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA
- Author
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Charles Marcaillou, Pierre-Simon Jouk, Françoise Clerget-Darpoux, Joelle Chastang, Sheela Nampoothiri, Emmanuel Tubacher, Renaud Touraine, Audrey Labalme, Francis Rousseau, Patrick Edery, Annick Toutain, Mourad Sahbatou, Carol Wise, Faiza Senni, Anne-Louise Leutenegger, Elisabeth Steichen, Siren Berland, Damien Sanlaville, Michael B. Bober, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Service de Cytogenetique Constitutionnelle, Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, Amrita Institute of Medical Sciences and Research Center, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), DYCTIM, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Registre des Handicaps de l'Enfant et Observatoire Périnatal Isère, RHEOP-RHEOP, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, INTEGRAGEN, IntegraGen, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), and Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Spliceosome ,MESH: Pedigree ,MESH: Introns ,[SDV]Life Sciences [q-bio] ,MESH: Base Pairing ,MESH: Fetal Growth Retardation ,MESH: Chromosomes, Human, Pair 2 ,Prp24 ,MESH: RNA Splice Sites ,Biology ,MESH: Microcephaly ,MESH: RNA, Small Nuclear ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Minor spliceosome ,snRNP ,MESH: Dwarfism ,030304 developmental biology ,MESH: Point Mutation ,Genetics ,0303 health sciences ,Multidisciplinary ,MESH: Humans ,urogenital system ,MESH: Child, Preschool ,Intron ,MESH: Osteochondrodysplasias ,MESH: Infant ,[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation ,MESH: Male ,MESH: Cell Line ,MESH: Microtubule-Associated Proteins ,MESH: Nucleic Acid Conformation ,RNA splicing ,MESH: Inverted Repeat Sequences ,MESH: RNA Splicing ,MESH: Female ,030217 neurology & neurosurgery ,Small nuclear RNA ,MESH: Spliceosomes - Abstract
International audience; The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for protein translation. We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no. 210710]. Expression of a subgroup of genes, possibly linked to the disease phenotype, and minor intron splicing were affected in cell lines derived from TALS patients. Our findings demonstrate a crucial role of the minor spliceosome component U4atac snRNA in early human development and postnatal survival.
- Published
- 2011
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