Hospices Civils de Lyon, Service de Cytogénétique Constitutionnelle, Bron, F-69677, France.
Science. 2011 Apr 8;332(6026):240-3. doi: 10.1126/science.1202205.
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.
剪接体是一种包含蛋白质和小核 RNA（snRNA）的核糖核蛋白复合物，通过内含子切除和外显子连接催化 RNA 剪接，产生成熟的信使 RNA，后者又作为蛋白质翻译的模板。我们在脑骨畸形和不明原因产后死亡患者的小剪接体的 U4atac snRNA 成分中发现了四个点突变[小头骨发育不良性原基性侏儒症 1 型（MOPD1）或 Taybi-Linder 综合征（TALS）；孟德尔遗传在线粒体 ID 号 210710]。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和小内含子剪接受到影响。我们的研究结果表明，小剪接体成分 U4atac snRNA 在人类早期发育和产后存活中起着至关重要的作用。
