Files in this item
Transcriptionally correlated subcellular dynamics of MBNL1 during lens development and their implication for the molecular pathology of myotonic dystrophy type 1
Item metadata
dc.contributor.author | Coleman, Stewart | |
dc.contributor.author | Prescott, Alan R. | |
dc.contributor.author | Sleeman, Judith Elizabeth | |
dc.date.accessioned | 2014-10-24T11:31:04Z | |
dc.date.available | 2014-10-24T11:31:04Z | |
dc.date.issued | 2014-03-01 | |
dc.identifier.citation | Coleman , S , Prescott , A R & Sleeman , J E 2014 , ' Transcriptionally correlated subcellular dynamics of MBNL1 during lens development and their implication for the molecular pathology of myotonic dystrophy type 1 ' , Biochemical Journal , vol. 458 , no. 2 , pp. 267-280 . https://doi.org/10.1042/BJ20130870 | en |
dc.identifier.issn | 0264-6021 | |
dc.identifier.other | PURE: 102871243 | |
dc.identifier.other | PURE UUID: 7436593e-cd9f-415f-a2da-480a7e17090e | |
dc.identifier.other | Scopus: 84894254702 | |
dc.identifier.other | ORCID: /0000-0003-0345-6508/work/60426886 | |
dc.identifier.other | WOS: 000333718300009 | |
dc.identifier.uri | https://hdl.handle.net/10023/5573 | |
dc.description | This work is supported by the Scottish Universities Life Science Alliance (SULSA) and the Biotechnology and Biological Sciences Research Council (BBSRC) via a Ph.D. studentship to S.M.C. | en |
dc.description.abstract | DM1 (myotonic dystrophy type 1) is caused by elongation of a CTG repeat in the DMPK (dystrophia myotonica-protein kinase) gene. mRNA transcripts containing these CUGexp (CUG expansion) repeats form accumulations, or foci, in the nucleus of the cell. The pathogenesis of DM1 is proposed to result from inappropriate patterns of alternative splicing caused by sequestration of the developmentally regulated alternative splicing factor MBNL1 (muscleblind-like 1) by these foci. Since eye lens cataract is a common feature of DM1 we have examined the distribution and dynamics of MBNL1 in lens epithelial cell lines derived from patients with DM1. The results of the present study demonstrate that only a small proportion of nuclear MBNL1 accumulates in CUGexp pre-mRNA foci. MBNL1 is, however, highly mobile and changes localization in response to altered transcription and splicing activity. Moreover, immunolocalization studies in lens sections suggest that a change in MBNL1 distribution is important during lens growth and differentiation. Although these data suggest that the loss of MBNL1 function due to accumulation in foci is an unlikely explanation for DM1 symptoms in the lens, they do demonstrate a strong relationship between the subcellular MBNL1 localization and pathways of cellular differentiation, providing an insight into the sensitivity of the lens to changes in MBNL1 distribution. | |
dc.format.extent | 13 | |
dc.language.iso | eng | |
dc.relation.ispartof | Biochemical Journal | en |
dc.rights | © The Authors. 2014. Journal compilation © 2014 Biochemical Society. | en |
dc.subject | Differentiation | en |
dc.subject | Lens epithelium | en |
dc.subject | Muscleblind-like 1 (MBNL1) | en |
dc.subject | Myotonic dystrophy type 1 (DM1) | en |
dc.subject | Nuclear dynamics | en |
dc.subject | Splicing speckles | en |
dc.subject | QP Physiology | en |
dc.subject | QH301 Biology | en |
dc.subject.lcc | QP | en |
dc.subject.lcc | QH301 | en |
dc.title | Transcriptionally correlated subcellular dynamics of MBNL1 during lens development and their implication for the molecular pathology of myotonic dystrophy type 1 | en |
dc.type | Journal article | en |
dc.description.version | Postprint | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1042/BJ20130870 | |
dc.description.status | Peer reviewed | en |
This item appears in the following Collection(s)
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.