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dc.contributor.authorHerdy, Barbaraen
dc.contributor.authorMayer, Clemensen
dc.contributor.authorVarshney, Dhavalen
dc.contributor.authorMarsico, Giovannien
dc.contributor.authorMurat, Pierreen
dc.contributor.authorTaylor, Chrisen
dc.contributor.authorD'Santos, Cliveen
dc.contributor.authorTannahill, Daviden
dc.contributor.authorBalasubramanian, Shankaren
dc.date.accessioned2018-11-17T00:31:30Z
dc.date.available2018-11-17T00:31:30Z
dc.date.issued2018-11en
dc.identifier.issn0305-1048
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285369
dc.description.abstractRNA G-quadruplexes (rG4s) are secondary structures in mRNAs known to influence RNA post-transcriptional mechanisms thereby impacting neurodegenerative disease and cancer. A detailed knowledge of rG4-protein interactions is vital to enable the understanding of rG4 function. Herein, we describe a systematic, unbiased affinity proteomics approach that identified 80 high-confidence interactors that assemble on the rG4 located in the 5’untranslated region (UTR) of the NRAS oncogene. Novel rG4 interactors included DDX3X, DDX5, DDX17, GRSF1 and NSUN5. The majority of identified proteins contained a glycine-arginine (GAR) domain and notably GAR-domain mutation in DDX3X and DDX17 abrogated rG4 binding. Identification of DDX3X targets by transcriptome-wide individual-nucleotide resolution UV-crosslinking and affinity enrichment (iCLAE) revealed a striking association with 5’UTR rG4-containing transcripts which was reduced upon GAR-domain mutation. Our work highlights hitherto unrecognized features of rG4 structure-protein interactions that highlight new roles of rG4 structures in mRNA post-transcriptional control.
dc.description.sponsorshipERC
dc.format.mediumPrinten
dc.languageengen
dc.publisherOxford University Press
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHela Cellsen
dc.subjectCytoplasmen
dc.subjectHumansen
dc.subjectRNA, Messengeren
dc.subject5' Untranslated Regionsen
dc.subjectReproducibility of Resultsen
dc.subjectGenes, rasen
dc.subjectDEAD-box RNA Helicasesen
dc.subjectG-Quadruplexesen
dc.subjectProtein Domainsen
dc.titleAnalysis of NRAS RNA G-quadruplex binding proteins reveals DDX3X as a novel interactor of cellular G-quadruplex containing transcripts.en
dc.typeArticle
prism.endingPage11604
prism.issueIdentifier21en
prism.publicationDate2018en
prism.publicationNameNucleic acids researchen
prism.startingPage11592
prism.volume46en
dc.identifier.doi10.17863/CAM.32735
dcterms.dateAccepted2018-09-12en
rioxxterms.versionofrecord10.1093/nar/gky861en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-11en
dc.contributor.orcidTannahill, David [0000-0002-3811-6864]
dc.contributor.orcidBalasubramanian, Shankar [0000-0002-0281-5815]
dc.identifier.eissn1362-4962
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (CB4330)
pubs.funder-project-idEuropean Research Council (339778)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (702476)


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