|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0008073,
umls-concept:C0026882,
umls-concept:C0035709,
umls-concept:C0162771,
umls-concept:C0205165,
umls-concept:C0449432,
umls-concept:C1179435,
umls-concept:C1524073,
umls-concept:C1548799,
umls-concept:C1705248,
umls-concept:C1832361,
umls-concept:C1859452
|
|
pubmed:issue |
6026
|
|
pubmed:dateCreated |
2011-4-8
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
1095-9203
|
|
pubmed:author |
pubmed-author:AkagiKeikoK,
pubmed-author:AlbrechtBeateB,
pubmed-author:AlderHansjuergH,
pubmed-author:DietrichRosemary CRC,
pubmed-author:FuY PYP,
pubmed-author:HaanEricE,
pubmed-author:HeHuilingH,
pubmed-author:LiJingfengJ,
pubmed-author:LiyanarachchiSandyaS,
pubmed-author:NagyRebeccaR,
pubmed-author:PadgettRichard ARA,
pubmed-author:PuffenbergerErikE,
pubmed-author:SebastianNikhilN,
pubmed-author:SinghJarnailJ,
pubmed-author:SymerDavid EDE,
pubmed-author:WangHengH,
pubmed-author:WenBernardB,
pubmed-author:WestmanJudith AJA,
pubmed-author:WieczorekDagmarD,
pubmed-author:XinBaozhongB,
pubmed-author:YanPearllyP,
pubmed-author:de la ChapelleAlbertA
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
8
|
|
pubmed:volume |
332
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
238-40
|
|
pubmed:dateRevised |
2011-6-13
|
|
pubmed:meshHeading |
pubmed-meshheading:21474760-Cell Line,
pubmed-meshheading:21474760-Chromosomes, Human, Pair 2,
pubmed-meshheading:21474760-Dwarfism,
pubmed-meshheading:21474760-Female,
pubmed-meshheading:21474760-Fetal Growth Retardation,
pubmed-meshheading:21474760-Humans,
pubmed-meshheading:21474760-Introns,
pubmed-meshheading:21474760-Inverted Repeat Sequences,
pubmed-meshheading:21474760-Male,
pubmed-meshheading:21474760-Microcephaly,
pubmed-meshheading:21474760-Mutation,
pubmed-meshheading:21474760-Nucleic Acid Conformation,
pubmed-meshheading:21474760-Osteochondrodysplasias,
pubmed-meshheading:21474760-Pedigree,
pubmed-meshheading:21474760-RNA, Small Nuclear,
pubmed-meshheading:21474760-RNA Splicing,
pubmed-meshheading:21474760-Spliceosomes
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I.
|
|
pubmed:affiliation |
Human Cancer Genetics Program, Ohio State University, Columbus, OH 43210, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
