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dc.contributor.authorCarlile, Thomas M.
dc.contributor.authorZinshteyn, Boris
dc.contributor.authorShin, Hakyung
dc.contributor.authorBartoli, Kristen Marie
dc.contributor.authorGilbert, Wendy
dc.contributor.authorRojas Duran, Maria Fernanda
dc.date.accessioned2015-05-08T18:53:45Z
dc.date.available2015-05-08T18:53:45Z
dc.date.issued2014-09
dc.date.submitted2014-05
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.urihttp://hdl.handle.net/1721.1/96947
dc.description.abstractPost-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function—it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.en_US
dc.description.sponsorshipAmerican Cancer Society (Robbie Sue Mudd Kidney Cancer Research Scholar Grant RSG-13-396-01-RMC)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (GM094303)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (GM081399)en_US
dc.description.sponsorshipAmerican Cancer Society. New England Division (Ellison Foundation Postdoctoral Fellowship)en_US
dc.description.sponsorshipAmerican Cancer Society (Postdoctoral Fellowship PF-13-319-01-RMC)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Pre-doctoral Training Grant T32GM007287)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nature13802en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titlePseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cellsen_US
dc.typeArticleen_US
dc.identifier.citationCarlile, Thomas M., Maria F. Rojas-Duran, Boris Zinshteyn, Hakyung Shin, Kristen M. Bartoli, and Wendy V. Gilbert. “Pseudouridine Profiling Reveals Regulated mRNA Pseudouridylation in Yeast and Human Cells.” Nature 515, no. 7525 (September 5, 2014): 143–146.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorCarlile, Thomas M.en_US
dc.contributor.mitauthorRojas Duran, Maria F.en_US
dc.contributor.mitauthorZinshteyn, Borisen_US
dc.contributor.mitauthorShin, Hakyungen_US
dc.contributor.mitauthorBartoli, Kristen Marieen_US
dc.contributor.mitauthorGilbert, Wendyen_US
dc.relation.journalNatureen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCarlile, Thomas M.; Rojas-Duran, Maria F.; Zinshteyn, Boris; Shin, Hakyung; Bartoli, Kristen M.; Gilbert, Wendy V.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7699-9354
dc.identifier.orcidhttps://orcid.org/0000-0003-0036-7307
dc.identifier.orcidhttps://orcid.org/0000-0003-2807-9657
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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