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Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I.
Science 2011; 332(6026):238-40Sci

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.

Authors+Show Affiliations

Human Cancer Genetics Program, Ohio State University, Columbus, OH 43210, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21474760

Citation

He, Huiling, et al. "Mutations in U4atac snRNA, a Component of the Minor Spliceosome, in the Developmental Disorder MOPD I." Science (New York, N.Y.), vol. 332, no. 6026, 2011, pp. 238-40.
He H, Liyanarachchi S, Akagi K, et al. Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. Science. 2011;332(6026):238-40.
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 (New York, N.Y.), 332(6026), pp. 238-40. doi:10.1126/science.1200587.
He H, et al. Mutations in U4atac snRNA, a Component of the Minor Spliceosome, in the Developmental Disorder MOPD I. Science. 2011 Apr 8;332(6026):238-40. PubMed PMID: 21474760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. AU - He,Huiling, AU - Liyanarachchi,Sandya, AU - Akagi,Keiko, AU - Nagy,Rebecca, AU - Li,Jingfeng, AU - Dietrich,Rosemary C, AU - Li,Wei, AU - Sebastian,Nikhil, AU - Wen,Bernard, AU - Xin,Baozhong, AU - Singh,Jarnail, AU - Yan,Pearlly, AU - Alder,Hansjuerg, AU - Haan,Eric, AU - Wieczorek,Dagmar, AU - Albrecht,Beate, AU - Puffenberger,Erik, AU - Wang,Heng, AU - Westman,Judith A, AU - Padgett,Richard A, AU - Symer,David E, AU - de la Chapelle,Albert, PY - 2011/4/9/entrez PY - 2011/4/9/pubmed PY - 2011/4/22/medline SP - 238 EP - 40 JF - Science (New York, N.Y.) JO - Science VL - 332 IS - 6026 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/21474760/Mutations_in_U4atac_snRNA_a_component_of_the_minor_spliceosome_in_the_developmental_disorder_MOPD_I_ L2 - http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=21474760 DB - PRIME DP - Unbound Medicine ER -