Association of TALS Developmental Disorder with Defect in Minor Splicing Component U4atac snRNA

被引：161

作者：

Edery, Patrick ^{[1
,2
,3
,4
,5
]}

Marcaillou, Charles ^{[6
]}

Sahbatou, Mourad ^{[7
]}

Labalme, Audrey ^{[1
]}

Chastang, Joelle ^{[1
]}

Touraine, Renaud ^{[8
]}

Tubacher, Emmanuel ^{[7
]}

Senni, Faiza ^{[1
]}

Bober, Michael B. ^{[9
]}

Nampoothiri, Sheela ^{[10
]}

Jouk, Pierre-Simon ^{[11
,12
]}

Steichen, Elisabeth ^{[13
]}

Berland, Siren ^{[14
,15
]}

Toutain, Annick ^{[16
,17
]}

Wise, Carol A. ^{[18
]}

Sanlaville, Damien ^{[1
,2
,3
,4
,5
]}

Rousseau, Francis ^{[6
]}

Clerget-Darpoux, Francoise ^{[19
,20
]}

Leutenegger, Anne-Louise ^{[21
,22
]}

机构：

[1] Hosp Civils Lyon, Serv Cytogenet Constitut, F-69677 Bron, France

[2] INSERM, U1028, F-69000 Lyon, France

[3] CNRS, UMR5292, F-69000 Lyon, France

[4] Univ Lyon 1, F-69000 Lyon, France

[5] Ctr Rech Neurosci Lyon, Translat & Integrat Grp Epilepsy Res, F-69000 Lyon, France

[6] IntegraGen, F-91030 Evry, France

[7] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, F-75010 Paris, France

[8] Hop Nord St Etienne, CHU, Serv Genet, F-42055 St Etienne, France

[9] Alfred I DuPont Hosp Children, Dept Pediat, Div Med Genet, Wilmington, DE 19803 USA

[10] Amrita Inst Med Sci & Res Ctr, Dept Pediat Genet, Cochin 682041, Kerala, India

[11] CHU Grenoble, Dept Genet & Procreat, F-38043 Grenoble 9, France

[12] Univ Grenoble 1, CNRS, UMR 5525, F-38041 Grenoble, France

[13] Univ Innsbruck Hosp, Dept Pediat, A-6020 Innsbruck, Austria

[14] St Olavs Hosp, Dept Pathol, Clin Genet Sect, N-7006 Trondheim, Norway

[15] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

[16] Hop Bretonneau, CHRU, Serv Genet, F-37044 Tours, France

[17] Univ Tours, INSERM, U930, Tours, France

[18] Texas Scottish Rite Hosp Children, Ctr Musculoskeletal Res, Dallas, TX 75219 USA

[19] INSERM, U669, F-94804 Villejuif, France

[20] Univ Paris 11, UMR S669, F-94804 Villejuif, France

[21] INSERM, U946, F-75010 Paris, France

[22] Univ Paris Diderot, Inst Univ Hematol, UMR S946, F-75010 Paris, France

来源：

SCIENCE | 2011年 / 332卷 / 6026期

关键词：

NONSENSE-MEDIATED DECAY; INBREEDING COEFFICIENT; RNA SURVEILLANCE; U4; SNRNA; PROTEIN; INTRONS; U12-TYPE; SPLICEOSOME; DWARFISM;

D O I：

10.1126/science.1202205

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：240 / 243

页数：4

共 21 条

[1] U12DB: a database of orthologous U12-type spliceosomal introns [J].