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dc.contributor.authorSithole, Nyarieen
dc.contributor.authorWilliams, Claire Aen
dc.contributor.authorVaughan, Aisling Men
dc.contributor.authorKenyon, Juliaen
dc.contributor.authorLever, Andrewen
dc.date.accessioned2018-09-10T22:16:16Z
dc.date.available2018-09-10T22:16:16Z
dc.date.issued2018-09en
dc.identifier.issn0022-2836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280044
dc.description.abstractHIV splicing involves 5 splice donor and 8 splice acceptor sequences which, together with cryptic splice sites, generate over 100 mRNA species. 90% of both partially spliced and fully spliced transcripts utilise the intrinsically weak A4/A5 3’ splice site cluster. We show that DDX17, but not its close paralog DDX5, specifically controls the usage of this splice acceptor group. In its absence production of the viral envelope protein and other regulatory and accessory proteins are grossly reduced whilst Vif, which uses the A1 splice acceptor is unaffected. This is associated with a profound decrease in viral export from the cell. Loss of Vpu expression causing upregulation of cellular Tetherin compounds the phenotype. DDX17 utilises distinct RNA binding motifs for its role in efficient HIV replication and we identify RNA binding motifs essential for its role whilst the Walker A, Walker B (DEAD), Q motif and the glycine doublet motif are all dispensable. We show that DDX17 interacts with SRSF1/SF2 and the heterodimeric auxiliary factor U2AF65/35 which are essential splicing factors in the generation of Rev and Env/Vpu transcripts.
dc.description.sponsorshipWellcome Trust , Cambridge Biomedical Research Centre and Clinical Academic Reserve
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCells, Cultureden
dc.subjectCell Line, Tumoren
dc.subjectHumansen
dc.subjectHIV-1en
dc.subjectHIV Infectionsen
dc.subjectRNA Splice Sitesen
dc.subjectGene Expression Regulation, Viralen
dc.subjectAlternative Splicingen
dc.subjectAmino Acid Motifsen
dc.subjectProtein Bindingen
dc.subjectDEAD-box RNA Helicasesen
dc.subjectProtein Interaction Domains and Motifsen
dc.subjectGene Knockdown Techniquesen
dc.titleDDX17 Specifically, and Independently of DDX5, Controls Use of the HIV A4/5 Splice Acceptor Cluster and Is Essential for Efficient Replication of HIV.en
dc.typeArticle
prism.endingPage3128
prism.issueIdentifier18 Pt Ben
prism.publicationDate2018en
prism.publicationNameJournal of molecular biologyen
prism.startingPage3111
prism.volume430en
dc.identifier.doi10.17863/CAM.27408
dcterms.dateAccepted2018-06-27en
rioxxterms.versionofrecord10.1016/j.jmb.2018.06.052en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-09en
dc.contributor.orcidKenyon, Julia [0000-0001-6055-7052]
dc.identifier.eissn1089-8638
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (097223/Z/11/Z)


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