File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Perturbation of U2AF65/NXF1-mediated RNA nuclear export enhances RNA toxicity in polyQ diseases

TitlePerturbation of U2AF65/NXF1-mediated RNA nuclear export enhances RNA toxicity in polyQ diseases
Authors
Issue Date2011
Citation
Human Molecular Genetics, 2011, v. 20, n. 19, p. 3787-3797 How to Cite?
AbstractExpanded CAG RNA has recently been reported to contribute to neurotoxicity in polyglutamine (polyQ) degeneration. In this study, we showed that RNA carrying an expanded CAG repeat progressively accumulated in the cell nucleus of transgenic Drosophila that displayed degeneration. Our gene knockdown and mutant analyses demonstrated that reduction of U2AF50 function, a gene involved in RNA nuclear export, intensified nuclear accumulation of expanded CAG RNA and resulted in a concomitant exacerbation of expanded CAG RNA-mediated toxicity in vivo. We found that the human U2AF50 ortholog, U2AF65, interacted directly and specifically with expanded CAG RNA via its RRM3 domain. We further identified an RNA/protein complex that consisted of expanded CAG RNA, U2AF65 and the NXF1 nuclear export receptor. The U2AF65 protein served as an adaptor to link expanded CAG RNA to NXF1 for RNA export. Finally, we confirmed the nuclear accumulation of expanded CAG RNA in symptomatic polyQ transgenic mice and also observed a neurodevelopmental downregulation of U2AF65 protein levels in mice. Altogether, our findings demonstrate that the cell nucleus is a site where expanded CAG RNA exerts its toxicity. We also provide a novel mechanistic explanation to how perturbation of RNA nuclear export would contribute to polyQ degeneration. © The Author 2011. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/336095
ISSN
2023 Impact Factor: 3.1
2023 SCImago Journal Rankings: 1.602
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTsoi, Ho-
dc.contributor.authorLau, Chi Kong-
dc.contributor.authorLau, Kwok Fai-
dc.contributor.authorChan, Ho Yin Edwin-
dc.date.accessioned2024-01-15T08:23:23Z-
dc.date.available2024-01-15T08:23:23Z-
dc.date.issued2011-
dc.identifier.citationHuman Molecular Genetics, 2011, v. 20, n. 19, p. 3787-3797-
dc.identifier.issn0964-6906-
dc.identifier.urihttp://hdl.handle.net/10722/336095-
dc.description.abstractExpanded CAG RNA has recently been reported to contribute to neurotoxicity in polyglutamine (polyQ) degeneration. In this study, we showed that RNA carrying an expanded CAG repeat progressively accumulated in the cell nucleus of transgenic Drosophila that displayed degeneration. Our gene knockdown and mutant analyses demonstrated that reduction of U2AF50 function, a gene involved in RNA nuclear export, intensified nuclear accumulation of expanded CAG RNA and resulted in a concomitant exacerbation of expanded CAG RNA-mediated toxicity in vivo. We found that the human U2AF50 ortholog, U2AF65, interacted directly and specifically with expanded CAG RNA via its RRM3 domain. We further identified an RNA/protein complex that consisted of expanded CAG RNA, U2AF65 and the NXF1 nuclear export receptor. The U2AF65 protein served as an adaptor to link expanded CAG RNA to NXF1 for RNA export. Finally, we confirmed the nuclear accumulation of expanded CAG RNA in symptomatic polyQ transgenic mice and also observed a neurodevelopmental downregulation of U2AF65 protein levels in mice. Altogether, our findings demonstrate that the cell nucleus is a site where expanded CAG RNA exerts its toxicity. We also provide a novel mechanistic explanation to how perturbation of RNA nuclear export would contribute to polyQ degeneration. © The Author 2011. Published by Oxford University Press. All rights reserved.-
dc.languageeng-
dc.relation.ispartofHuman Molecular Genetics-
dc.titlePerturbation of U2AF65/NXF1-mediated RNA nuclear export enhances RNA toxicity in polyQ diseases-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/hmg/ddr297-
dc.identifier.pmid21725067-
dc.identifier.scopuseid_2-s2.0-80052715145-
dc.identifier.volume20-
dc.identifier.issue19-
dc.identifier.spage3787-
dc.identifier.epage3797-
dc.identifier.eissn1460-2083-
dc.identifier.isiWOS:000294810000007-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats