Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

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datacite.contributor.supervisorsenior_editor: Zoghbi, Huda Y
datacite.contributor.supervisoreditor: Nakatogawa, Hitoshi
dc.contributor.authorNehammer, Camilla
dc.contributor.authorEjlerskov, Patrick
dc.contributor.authorGopal, Sandeep
dc.contributor.authorHandley, Ava
dc.contributor.authorNg, Leelee
dc.contributor.authorMoreira, Pedro
dc.contributor.authorLee, Huikyong
dc.contributor.authorIssazadeh-Navikas, Shohreh
dc.contributor.authorRubinsztein, David C
dc.contributor.authorPocock, Roger
dc.contributor.orcidHandley, Ava [0000-0003-1543-1551]
dc.contributor.orcidRubinsztein, David C [0000-0001-5002-5263]
dc.contributor.orcidPocock, Roger [0000-0002-5515-3608]
dc.date.accessioned2019-12-17T05:05:00Z
dc.date.available2019-12-17T05:05:00Z
dc.date.issued2019-12-04
dc.date.submitted2019-07-04
dc.date.updated2019-12-17T05:04:59Z
dc.description.abstractAppropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.
dc.identifier.doi10.17863/CAM.47080
dc.identifier.eissn2050-084X
dc.identifier.other49930
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/300008
dc.languageen
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectBiochemistry and Chemical Biology
dc.subjectGenetics and Genomics
dc.subjectmicroRNA
dc.subjectautophagy
dc.subjectprotein aggregation
dc.subjectmammalian cells
dc.subjecthuman cells
dc.subjectC. elegans
dc.titleInterferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
dc.typeArticle
dcterms.dateAccepted2019-12-03
pubs.funder-project-idNational Health and Medical Research Council (GNT1137645)
pubs.funder-project-idLundbeckfonden (R223-2016-849)
pubs.funder-project-idLundbeckfonden (R210-2015-3372)
pubs.funder-project-idWellcome (095317/Z/11/Z)
pubs.funder-project-idDet Frie Forskningsråd (DFF-6110-00461)
pubs.funder-project-idVeski (VIF23)
pubs.funder-project-idDet Frie Forskningsråd (DFF-6110–00658)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.7554/elife.49930
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