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dc.contributor.authorClelland, Allyson Kara
dc.contributor.authorBales, Alexandra Beatrice Elizabeth
dc.contributor.authorSleeman, Judith Elizabeth
dc.date.accessioned2012-06-12T13:31:03Z
dc.date.available2012-06-12T13:31:03Z
dc.date.issued2012-06-01
dc.identifier.citationClelland , A K , Bales , A B E & Sleeman , J E 2012 , ' Changes in intranuclear mobility of mature snRNPs provide a mechanism for splicing defects in spinal muscular atrophy ' Journal of Cell Science , vol 125 , no. 11 , pp. 2626-2637 . DOI: 10.1242/jcs.096867en
dc.identifier.issn0021-9533
dc.identifier.otherPURE: 21239792
dc.identifier.otherPURE UUID: ecd15b2d-0282-4398-9b3c-3038855bdb3d
dc.identifier.otherWOS: 000306705000009
dc.identifier.urihttp://hdl.handle.net/10023/2743
dc.descriptionThis work was funded by the Wellcome Trust (grant ID WT078810MA)en
dc.description.abstractIt is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of small nuclear ribonucleoproteins (snRNPs): essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intranuclear snRNP mobility, we employed a panel of inhibitors of different stages of pre-mRNA processing. This in vivo modelling demonstrates that snRNP mobility is altered directly as a result of impaired snRNP maturation. Current models of nuclear dynamics predict that subnuclear structures, including the spliceosome, form by self-organization mediated by stochastic interactions between their molecular components. Thus, alteration of the intranuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA.en
dc.format.extent12en
dc.language.isoeng
dc.relation.ispartofJournal of Cell Scienceen
dc.rights© 2012. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.en
dc.subjectsnRNPsen
dc.subjectSMAen
dc.subjectSMNen
dc.subjectnucleusen
dc.subjectQH301 Biologyen
dc.subject.lccQH301en
dc.titleChanges in intranuclear mobility of mature snRNPs provide a mechanism for splicing defects in spinal muscular atrophyen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttp://dx.doi.org/10.1242/jcs.096867
dc.description.statusPeer revieweden


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