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dc.contributor.authorBoutz, Paul
dc.contributor.authorJangi, Mohini
dc.contributor.authorSharp, Phillip A.
dc.contributor.authorPaul, Prakriti
dc.date.accessioned2014-12-01T17:07:58Z
dc.date.available2014-12-01T17:07:58Z
dc.date.issued2014-03
dc.date.submitted2014-01
dc.identifier.issn0890-9369
dc.identifier.issn1549-5477
dc.identifier.urihttp://hdl.handle.net/1721.1/91959
dc.description.abstractThe tight regulation of splicing networks is critical for organismal development. To maintain robust splicing patterns, many splicing factors autoregulate their expression through alternative splicing-coupled nonsense-mediated decay (AS-NMD). However, as negative autoregulation results in a self-limiting window of splicing factor expression, it is unknown how variations in steady-state protein levels can arise in different physiological contexts. Here, we demonstrate that Rbfox2 cross-regulates AS-NMD events within RNA-binding proteins to alter their expression. Using individual nucleotide-resolution cross-linking immunoprecipitation coupled to high-throughput sequencing (iCLIP) and mRNA sequencing, we identified >200 AS-NMD splicing events that are bound by Rbfox2 in mouse embryonic stem cells. These “silent” events are characterized by minimal apparent splicing changes but appreciable changes in gene expression upon Rbfox2 knockdown due to degradation of the NMD-inducing isoform. Nearly 70 of these AS-NMD events fall within genes encoding RNA-binding proteins, many of which are autoregulated. As with the coding splicing events that we found to be regulated by Rbfox2, silent splicing events are evolutionarily conserved and frequently contain the Rbfox2 consensus UGCAUG. Our findings uncover an unexpectedly broad and multilayer regulatory network controlled by Rbfox2 and offer an explanation for how autoregulatory splicing networks are tuned.en_US
dc.description.sponsorshipUnited States. Public Health Service (RO1-GM34277)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant CA112967)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)en_US
dc.description.sponsorshipDavid H. Koch Graduate Fellowshipen_US
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1101/gad.235770.113en_US
dc.rightsCreative Commons Attribution-Noncommericalen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0en_US
dc.titleRbfox2 controls autoregulation in RNA-binding protein networksen_US
dc.typeArticleen_US
dc.identifier.citationJangi, M., P. L. Boutz, P. Paul, and P. A. Sharp. “Rbfox2 Controls Autoregulation in RNA-Binding Protein Networks.” Genes & Development 28, no. 6 (March 15, 2014): 637–651.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorBoutz, Paulen_US
dc.contributor.mitauthorJangi, Mohinien_US
dc.contributor.mitauthorSharp, Phillip A.en_US
dc.contributor.mitauthorPaul, Prakritien_US
dc.relation.journalGenes & Developmenten_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.orderedauthorsJangi, Mohini; Boutz, Paul L.; Paul, Prakriti; Sharp, Phillip A.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1465-1691
mit.licensePUBLISHER_CCen_US


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