Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I
Date
2011
Authors
He, H.
Liyanarachchi, S.
Akagi, K.
Nagy, R.
Li, J.
Dietrich, R.
Li, W.
Sebastian, N.
Wen, B.
Xin, B.
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Journal article
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Science, 2011; 332(6026):238-240
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Huiling He... Eric Haan... et al.
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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.
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Copyright 2011 by the American Association for the Advancement of Science; all rights reserved.