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dc.contributor.authorLynch, DC
dc.contributor.authorRevil, T
dc.contributor.authorSchwartzentruber, J
dc.contributor.authorBhoj, EJ
dc.contributor.authorInnes, AM
dc.contributor.authorLamont, RE
dc.contributor.authorLemire, EG
dc.contributor.authorChodirker, BN
dc.contributor.authorTaylor, JP
dc.contributor.authorZackai, EH
dc.contributor.authorMcLeod, DR
dc.contributor.authorKirk, EP
dc.contributor.authorHoover-Fong, J
dc.contributor.authorFleming, L
dc.contributor.authorSavarirayan, R
dc.contributor.authorMajewski, J
dc.contributor.authorJerome-Majewska, LA
dc.contributor.authorParboosingh, JS
dc.contributor.authorBernier, FP
dc.date.accessioned2020-12-21T01:07:45Z
dc.date.available2020-12-21T01:07:45Z
dc.date.issued2014-07-01
dc.identifierpii: ncomms5483
dc.identifier.citationLynch, 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.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/256379
dc.description.abstractElucidating 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleDisrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome
dc.typeJournal Article
dc.identifier.doi10.1038/ncomms5483
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.source.titleNature Communications
melbourne.source.volume5
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1220245
melbourne.contributor.authorSavarirayan, Ravi
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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