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dc.contributor.authorHurt, Jessica A.
dc.contributor.authorRobertson, Alex De Jong
dc.contributor.authorBurge, Christopher B
dc.date.accessioned2014-02-07T17:41:01Z
dc.date.available2014-02-07T17:41:01Z
dc.date.issued2013-06
dc.date.submitted2013-03
dc.identifier.issn1088-9051
dc.identifier.urihttp://hdl.handle.net/1721.1/84683
dc.description.abstractUPF1 is a DNA/RNA helicase with essential roles in nonsense-mediated mRNA decay (NMD) and embryonic development. How UPF1 regulates target abundance and the relationship between NMD and embryogenesis are not well understood. To explore how NMD shapes the embryonic transcriptome, we integrated genome-wide analyses of UPF1 binding locations, NMD-regulated gene expression, and translation in murine embryonic stem cells (mESCs). We identified over 200 direct UPF1 binding targets using crosslinking/immunoprecipitation-sequencing (CLIP-seq) and revealed a repression pathway that involves 3′ UTR binding by UPF1 and translation but is independent of canonical targeting features involving 3′ UTR length and stop codon placement. Interestingly, NMD targeting of this set of mRNAs occurs in other mouse tissues and is conserved in human. We also show, using ribosome footprint profiling, that actively translated upstream open reading frames (uORFs) are enriched in transcription factor mRNAs and predict mRNA repression by NMD, while poorly translated mRNAs escape repression. Together, our results identify novel NMD determinants and targets and provide context for understanding the impact of UPF1 and NMD on the mESC transcriptome.en_US
dc.description.sponsorshipNational Institute of General Medical Sciences (U.S.) (Fellowship number F32GM0950)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH training grant)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (equipment grant no. 082139)en_US
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1101/gr.157354.113en_US
dc.rightsCreative Commons Attribution-Noncommercial 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en_US
dc.sourceGenome Researchen_US
dc.titleGlobal analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decayen_US
dc.typeArticleen_US
dc.identifier.citationHurt, J. A., A. D. Robertson, and C. B. Burge. “Global analyses of UPF1 binding and function reveal expanded scope of nonsense-mediated mRNA decay.” Genome Research 23, no. 10 (October 1, 2013): 1636-1650. © 2013, Cold Spring Harbor Laboratory Press.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorHurt, Jessica A.en_US
dc.contributor.mitauthorRobertson, Alex De Jongen_US
dc.contributor.mitauthorBurge, Christopher B.en_US
dc.relation.journalGenome Researchen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHurt, J. A.; Robertson, A. D.; Burge, C. B.en_US
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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