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dc.contributor.authorHoem, Gry
dc.contributor.authorLarsen, Kenneth Bowitz
dc.contributor.authorØvervatn, Aud Karin
dc.contributor.authorBrech, Andreas
dc.contributor.authorLamark, Trond
dc.contributor.authorSjøttem, Eva
dc.contributor.authorJohansen, Terje
dc.date.accessioned2019-10-07T11:02:30Z
dc.date.available2019-10-07T11:02:30Z
dc.date.issued2019-03-28
dc.description.abstractFragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG-repeat expansion in the 5′ UTR of the FMR1 gene on the X-chromosome. Both elevated levels of the expanded FMR1 mRNA and aberrant expression of a polyglycine protein (FMRpolyG) from the CGG-repeat region are hypothesized to trigger the pathogenesis of FXTAS. While increased expression of FMRpolyG leads to higher toxicity in FXTAS models, the pathogenic effect of this protein has only been studied in the presence of CGG-containing mRNA. Here we present a model that allows measurement of the effect of FMRpolyG-expression without co-expression of the corresponding CGG mRNA hairpin. This allows direct comparison of the effect of the FMRpolyG protein <i>per se</i>, vs. that of the FMRpolyG protein together with the CGG mRNA hairpin. Our results show that expression of the FMRpolyG, in the absence of any CGG mRNA, is sufficient to cause reduced cell viability, lamin ring disruption and aggregate formation. Furthermore, we found FMRpolyG to be a long-lived protein degraded primarily by the ubiquitin-proteasome-system. Together, our data indicate that accumulation of FMRpolyG protein per se may play a major role in the development of FXTAS.en_US
dc.description.sponsorshipUiT The Arctic University of Norwayen_US
dc.descriptionSource at <a href=https://doi.org/10.3389/fgene.2019.00249>https://doi.org/10.3389/fgene.2019.00249</a>.en_US
dc.identifier.citationHoem, G., Larsen, K.B., Øvervatn, A., Brech, A., Lamark, T., Sjøttem, E. & Johansen, T. (2019). The FMRpolyGlycine protein mediates aggregate formation and toxicity independent of the CGG mRNA hairpin in a cellular model for FXTAS. <i>Frontiers in Genetics, 10</i>, 249. https://doi.org/10.3389/fgene.2019.00249en_US
dc.identifier.cristinIDFRIDAID 1706768
dc.identifier.doi10.3389/fgene.2019.00249
dc.identifier.issn1664-8021
dc.identifier.urihttps://hdl.handle.net/10037/16340
dc.language.isoengen_US
dc.publisherFontiers Mediaen_US
dc.relation.journalFrontiers in Genetics
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/249884/Norway/Autophagy-regulated Signalosomes in Cellular Stress and Disease Pathways//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Genetics and genomics: 474en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474en_US
dc.subjectFXTASen_US
dc.subjectCGG repeat expansionen_US
dc.subjectRNA hairpinen_US
dc.subjectRAN translationen_US
dc.subjectpolyglycineen_US
dc.subjectprotein degradationen_US
dc.titleThe FMRpolyGlycine protein mediates aggregate formation and toxicity independent of the CGG mRNA hairpin in a cellular model for FXTASen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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