Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD i

Huiling He, Sandya Liyanarachchi, Keiko Akagi, Rebecca Nagy, Jingfeng Li, Rosemary Dietrich, Wei Li, Nikhil Sebastian, Bernard Wen, Baozhong Xin, Jarnail Singh, Pearlly Yan, Hansjuerg Alder, Eric Haan, Dagmar Wieczorek, Beate Albrecht, Erik Puffenberger, Heng Wang, Judith Westman, Richard PadgettDavid Symer, Albert de la Chapelle

    Research output: Contribution to journalArticlepeer-review

    168 Citations (Scopus)


    Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G>A, 51G>A, 55G>A, and 111G>A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.

    Original languageEnglish
    Pages (from-to)238-240
    Number of pages3
    Issue number6026
    Publication statusPublished - 8 Apr 2011

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    Copyright 2011 Elsevier B.V., All rights reserved.


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