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dc.contributor.authorSzkop, KJ
dc.contributor.authorCooke, PIC
dc.contributor.authorHumphries, JA
dc.contributor.authorKalna, V
dc.contributor.authorMoss, DS
dc.contributor.authorSchuster, EF
dc.contributor.authorNobeli, I
dc.date.accessioned2019-03-04T14:44:12Z
dc.date.issued2017-01
dc.identifier.citationFrontiers in molecular neuroscience, 2017, 10 pp. 279 - ?
dc.identifier.issn1662-5099
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3117
dc.identifier.eissn1662-5099
dc.identifier.doi10.3389/fnmol.2017.00279
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.
dc.formatElectronic-eCollection
dc.format.extent279 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDysregulation of Alternative Poly-adenylation as a Potential Player in Autism Spectrum Disorder.
dc.typeJournal Article
dcterms.dateAccepted2017-08-17
rioxxterms.versionofrecord10.3389/fnmol.2017.00279
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfFrontiers in molecular neuroscience
pubs.declined2019-03-01T15:51:00.91+0000
pubs.notesNo embargo
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/Endocrine Therapy Resistance
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/Endocrine Therapy Resistance
pubs.publication-statusPublished
pubs.volume10
pubs.embargo.termsNo embargo
icr.researchteamEndocrine Therapy Resistanceen_US
dc.contributor.icrauthorSchuster, Eugeneen


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