Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Science. 2011 Apr 8;332(6026):238-40. doi: 10.1126/science.1200587.

Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I.

Author information

  • 1Human Cancer Genetics Program, Ohio State University, Columbus, OH 43210, USA.

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.

Comment in

PMID:
21474760
[PubMed - indexed for MEDLINE]
PMCID:
PMC3380448
Free PMC Article

Images from this publication.See all images (2)Free text

Fig. 1
Fig. 2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk