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https://hdl.handle.net/2440/68524
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Type: | Journal article |
Title: | Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I |
Author: | He, H. Liyanarachchi, S. Akagi, K. Nagy, R. Li, J. Dietrich, R. Li, W. Sebastian, N. Wen, B. Xin, B. Singh, J. Yan, P. Alder, H. Haan, E. Wieczorek, D. Albrecht, B. Puffenberger, E. Wang, H. Westman, J. Padgett, R. et al. |
Citation: | Science, 2011; 332(6026):238-240 |
Publisher: | Amer Assoc Advancement Science |
Issue Date: | 2011 |
ISSN: | 0036-8075 1095-9203 |
Statement of Responsibility: | Huiling He... Eric Haan... et al. |
Abstract: | 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. |
Keywords: | Cell Line Chromosomes, Human, Pair 2 Spliceosomes Humans Dwarfism Osteochondrodysplasias Microcephaly Fetal Growth Retardation RNA, Small Nuclear Pedigree RNA Splicing Nucleic Acid Conformation Mutation Introns Female Male Inverted Repeat Sequences |
Rights: | Copyright 2011 by the American Association for the Advancement of Science; all rights reserved. |
DOI: | 10.1126/science.1200587 |
Published version: | http://dx.doi.org/10.1126/science.1200587 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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