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dc.contributor.authorSzkop, KJen_US
dc.contributor.authorCooke, PICen_US
dc.contributor.authorHumphries, JAen_US
dc.contributor.authorKalna, Ven_US
dc.contributor.authorMoss, DSen_US
dc.contributor.authorSchuster, EFen_US
dc.contributor.authorNobeli, Ien_US
dc.coverage.spatialSwitzerlanden_US
dc.date.accessioned2019-03-04T14:44:12Z
dc.date.issued2017en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28955198en_US
dc.identifier.citationFront Mol Neurosci, 2017, 10 pp. 279 - ?en_US
dc.identifier.issn1662-5099en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3117
dc.identifier.doi10.3389/fnmol.2017.00279en_US
dc.description.abstractWe present here the hypothesis that alternative poly-adenylation (APA) is dysregulated in the brains of individuals affected by Autism Spectrum Disorder (ASD), due to disruptions in the calcium signaling networks. APA, the process of selecting different poly-adenylation sites on the same gene, yielding transcripts with different-length 3' untranslated regions (UTRs), has been documented in different tissues, stages of development and pathologic conditions. Differential use of poly-adenylation sites has been shown to regulate the function, stability, localization and translation efficiency of target RNAs. However, the role of APA remains rather unexplored in neurodevelopmental conditions. In the human brain, where transcripts have the longest 3' UTRs and are thus likely to be under more complex post-transcriptional regulation, erratic APA could be particularly detrimental. In the context of ASD, a condition that affects individuals in markedly different ways and whose symptoms exhibit a spectrum of severity, APA dysregulation could be amplified or dampened depending on the individual and the extent of the effect on specific genes would likely vary with genetic and environmental factors. If this hypothesis is correct, dysregulated APA events might be responsible for certain aspects of the phenotypes associated with ASD. Evidence supporting our hypothesis is derived from standard RNA-seq transcriptomic data but we suggest that future experiments should focus on techniques that probe the actual poly-adenylation site (3' sequencing). To address issues arising from the use of post-mortem tissue and low numbers of heterogeneous samples affected by confounding factors (such as the age, gender and health of the individuals), carefully controlled in vitro systems will be required to model the effect of calcium signaling dysregulation in the ASD brain.en_US
dc.format.extent279 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectRNA–seqen_US
dc.subjectalternative poly-adenylationen_US
dc.subjectautism spectrum disorderen_US
dc.subjectcalcium signalingen_US
dc.subjecttranscriptionen_US
dc.titleDysregulation of Alternative Poly-adenylation as a Potential Player in Autism Spectrum Disorder.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-08-17en_US
rioxxterms.versionofrecord10.3389/fnmol.2017.00279en_US
rioxxterms.licenseref.startdate2017en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfFront Mol Neuroscien_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.publication-statusPublished onlineen_US
pubs.volume10en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorSchuster, Eugeneen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/