title: Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA.
abstract: 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.
authors.affiliation: Hospices Civils de Lyon, Service de Cytogénétique Constitutionnelle, Bron, F-69677, France. patrick.edery@chu-lyon.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Charles
authors.initials: C
authors.lastname: Marcaillou
authors.forename: Mourad
authors.initials: M
authors.lastname: Sahbatou
authors.forename: Audrey
authors.initials: A
authors.lastname: Labalme
authors.forename: Joelle
authors.initials: J
authors.lastname: Chastang
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tubacher
authors.forename: Faiza
authors.initials: F
authors.lastname: Senni
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bober
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Pierre-Simon
authors.initials: PS
authors.lastname: Jouk
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Steichen
authors.forename: Siren
authors.initials: S
authors.lastname: Berland
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wise
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Francis
authors.initials: F
authors.lastname: Rousseau
authors.forename: Françoise
authors.initials: F
authors.lastname: Clerget-Darpoux
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Leutenegger
mesh_terms: D020029:Base Pairing; D002460:Cell Line; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007438:Introns; D055029:Inverted Repeat Sequences; D008297:Male; D008831:Microcephaly / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009690:Nucleic Acid Conformation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation; D022821:RNA Splice Sites; D012326:RNA Splicing; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism
chemical_list: C497850:CLASP1 protein, human; D008869:Microtubule-Associated Proteins; D022821:RNA Splice Sites; D012342:RNA, Small Nuclear; C096986:U12 small nuclear RNA; C405482:U4 small nuclear RNA; C405486:U6 small nuclear RNA