Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome

Download
Author
Lynch, DC; Revil, T; Schwartzentruber, J; Bhoj, EJ; Innes, AM; Lamont, RE; Lemire, EG; Chodirker, BN; Taylor, JP; Zackai, EH; ...Date
2014-07-01Source Title
Nature CommunicationsPublisher
NATURE PUBLISHING GROUPUniversity of Melbourne Author/s
Savarirayan, RaviAffiliation
Paediatrics (RCH)Metadata
Show full item recordDocument Type
Journal ArticleCitations
Lynch, D. C., Revil, T., Schwartzentruber, J., Bhoj, E. J., Innes, A. M., Lamont, R. E., Lemire, E. G., Chodirker, B. N., Taylor, J. P., Zackai, E. H., McLeod, D. R., Kirk, E. P., Hoover-Fong, J., Fleming, L., Savarirayan, R., Majewski, J., Jerome-Majewska, L. A., Parboosingh, J. S. & Bernier, F. P. (2014). Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome. NATURE COMMUNICATIONS, 5 (1), https://doi.org/10.1038/ncomms5483.Access Status
Open AccessAbstract
Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.
Export Reference in RIS Format
Endnote
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
Refworks
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References