Association of TALS Developmental Disorder with Defect in Minor Splicing Component U4atac snRNA
Association of TALS Developmental Disorder with Defect in Minor Splicing Component U4atac snRNA
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DOI：
10.1126/science.1202205
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发表时间：
2011-04-08
期刊：
影响因子：
56.9
通讯作者：
Leutenegger, Anne-Louise
中科院分区：
文献类型：
--
作者：
Edery, Patrick;Marcaillou, Charles;Leutenegger, Anne-Louise
剪接体是一种核糖核蛋白复合物，包含蛋白质和小核RNA（snRNAs），它通过内含子切除和外显子连接来催化RNA剪接，从而产生成熟的信使RNA，而信使RNA反过来又作为蛋白质翻译的模板。我们在患有脑和骨骼畸形以及不明原因产后死亡[小头畸形骨发育不良性原始侏儒症1型（MOPD 1）或泰比 - 林德综合征（TALS）；人类孟德尔遗传编号210710]的患者的次要剪接体的U4atac snRNA成分中鉴定出四个点突变。在源自TALS患者的细胞系中，可能与疾病表型相关的一组基因的表达以及次要内含子剪接受到了影响。我们的研究结果表明次要剪接体成分U4atac snRNA在人类早期发育和产后生存中起着至关重要的作用。
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.