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 C. 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 A. Westman, Richard A. PadgettDavid E. Symer, Albert De La Chapelle

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)238-240
Number of pages3
JournalScience
Volume332
Issue number6026
DOIs
StatePublished - Apr 8 2011

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Spliceosomes
Small Nuclear RNA
Mutation
Introns
Multiple Abnormalities
RNA Splicing
High-Throughput Nucleotide Sequencing
Fetal Growth Retardation
Human Development
Fibroblasts
Type 1 Microcephalic osteodysplastic primordial dwarfism
Genes

ASJC Scopus subject areas

  • General

Cite this

He, H., Liyanarachchi, S., Akagi, K., Nagy, R., Li, J., Dietrich, R. C., ... De La Chapelle, A. (2011). Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD i. Science, 332(6026), 238-240. https://doi.org/10.1126/science.1200587

Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD i. / He, Huiling; Liyanarachchi, Sandya; Akagi, Keiko; Nagy, Rebecca; Li, Jingfeng; Dietrich, Rosemary C.; Li, Wei; Sebastian, Nikhil; Wen, Bernard; Xin, Baozhong; Singh, Jarnail; Yan, Pearlly; Alder, Hansjuerg; Haan, Eric; Wieczorek, Dagmar; Albrecht, Beate; Puffenberger, Erik; Wang, Heng; Westman, Judith A.; Padgett, Richard A.; Symer, David E.; De La Chapelle, Albert.

In: Science, Vol. 332, No. 6026, 08.04.2011, p. 238-240.

Research output: Contribution to journalArticle

He, H, Liyanarachchi, S, Akagi, K, Nagy, R, Li, J, Dietrich, RC, 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, JA, Padgett, RA, Symer, DE & De La Chapelle, A 2011, 'Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD i', Science, vol. 332, no. 6026, pp. 238-240. https://doi.org/10.1126/science.1200587
He, Huiling ; Liyanarachchi, Sandya ; Akagi, Keiko ; Nagy, Rebecca ; Li, Jingfeng ; Dietrich, Rosemary C. ; Li, Wei ; Sebastian, Nikhil ; Wen, Bernard ; Xin, Baozhong ; Singh, Jarnail ; Yan, Pearlly ; Alder, Hansjuerg ; Haan, Eric ; Wieczorek, Dagmar ; Albrecht, Beate ; Puffenberger, Erik ; Wang, Heng ; Westman, Judith A. ; Padgett, Richard A. ; Symer, David E. ; De La Chapelle, Albert. / Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD i. In: Science. 2011 ; Vol. 332, No. 6026. pp. 238-240.
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AU - Wang, Heng

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AU - Padgett, Richard A.

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AU - De La Chapelle, Albert

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