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dc.contributor.authorPark, So Jungen
dc.contributor.authorLee, Heejinen
dc.contributor.authorJo, Doo Sinen
dc.contributor.authorJo, Yoon Kyungen
dc.contributor.authorShin, Ji Hyunen
dc.contributor.authorKim, Han Byeolen
dc.contributor.authorSeo, Hae Mien
dc.contributor.authorRubinsztein, Daviden
dc.contributor.authorKoh, Jae-Youngen
dc.contributor.authorLee, Eun Kyungen
dc.contributor.authorCho, Dong-Hyungen
dc.date.accessioned2015-10-27T15:38:50Z
dc.date.available2015-10-27T15:38:50Z
dc.date.issued2015-10-28en
dc.identifier.citationBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2015, 1849(12): 1423–1431. doi:10.1016/j.bbagrm.2015.10.017en
dc.identifier.issn0006-3002
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252415
dc.description.abstractExcessive mitochondrial fission is associated with the pathogenesis of neurodegenerative diseases. Dynamin-related protein 1 (Drp1) possesses specific fission activity in mitochondria and peroxisomes. Various post-translational modifications of Drp1 are known to modulate complex mitochondrial dynamics. However, the posttranscriptional regulation of Drp1 remains poorly understood. Here, we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) regulates Drp1 expression at the post-transcriptional level. hnRNP A1 directly interacts with Drp1 mRNA at its 3'UTR region, and enhances translation potential without affecting mRNA stability. Down-regulation of hnRNP A1 induces mitochondrial elongation by reducing Drp1 expression. Moreover, depletion of hnRNP A1 suppresses 3-NP-medated mitochondrial fission and dysfunction. In contrast, over expression of hnRNP A1 promotes shortened mitochondrial length by increasing Drp1 expression. Additionally, hnRNP A1 significantly exacerbates 3-NP-induced mitochondrial dysfunction and cell death in neuroblastoma cells. Interestingly, treatment with 3-NP induces subcellular translocation of hnRNP A1 from the nucleus to the cytoplasm, which accelerates the increase in Drp1 expression in hnRNP A1 over expressing cells. Collectively, our findings suggest that hnRNP A1 controls mitochondrial dynamics by post-transcriptional regulation of Drp1.
dc.description.sponsorshipThis research was supported by a grant of the Korea–UK Collaborative Alzheimer's Disease Research Project by Ministry of Health & Welfare, Republic of Korea (A120196, HI14C1913) and was supported by the Basic Science Research Program of the National Research Foundation, Republic of Korea (2014R1A2A1A11053431). We are grateful to Wellcome Trust, Principal Research Fellowship to DCR (095317/Z/11/Z)
dc.languageEnglishen
dc.language.isoenen
dc.publisherElsevier
dc.rightsCreative Commons Attribution 4.0 International License
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleHeterogeneous nuclear ribonucleoprotein A1 post-transcriptionally regulates Drp1 expression in neuroblastoma cellsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.bbagrm.2015.10.017en
prism.endingPage1431
prism.publicationDate2015en
prism.publicationNameBBA - Gene Regulatory Mechanismsen
prism.startingPage1423
prism.volume1849en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectid095317/Z/11/Z
dcterms.dateAccepted2015-10-23en
rioxxterms.versionofrecord10.1016/j.bbagrm.2015.10.017en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-10-28en
dc.contributor.orcidRubinsztein, David [0000-0001-5002-5263]
dc.identifier.eissn1876-4320
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (095317/Z/11/A)
pubs.funder-project-idWellcome Trust (095317/Z/11/Z)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)


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Except where otherwise noted, this item's licence is described as Creative Commons Attribution 4.0 International License