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dc.contributor.authorHasan, Ayeshaen
dc.contributor.authorCotobal, Cristinaen
dc.contributor.authorDuncan, Caiaen
dc.contributor.authorMata, Juanen
dc.date.accessioned2014-10-07T08:26:31Z
dc.date.available2014-10-07T08:26:31Z
dc.date.issued2014-11-06en
dc.identifier.citationPLOS Genetics 2014, 10(11): e1004684. doi:10.1371/journal.pgen.1004684en
dc.identifier.issn1553-7390
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246128
dc.description.abstractmRNA half-lives are transcript-specific and vary over a range of more than 100-fold in eukaryotic cells. mRNA stabilities can be regulated by sequence-specific RNA-binding proteins (RBPs), which bind to regulatory sequence elements and modulate the interaction of the mRNA with the cellular RNA degradation machinery. However, it is unclear if this kind of regulation is sufficient to explain the large range of mRNA stabilities. To address this question we examined the transcriptome of 74 Schizosaccharomyces pombe strains carrying deletions in non-essential genes encoding predicted RBPs (86% of all such genes). We identified 25 strains that displayed changes in the levels of between 4 and 104 mRNAs. The putative targets of these RBPs formed biologically coherent groups, defining regulons involved in cell separation, ribosome biogenesis, meiotic progression, stress responses and mitochondrial function. Moreover, mRNAs in these groups were enriched in specific sequence motifs in their coding sequences and untranslated regions, suggesting that they are coregulated at the posttranscriptional level. We performed genome-wide RNA stability measurements for several RBP mutants, and confirmed that the altered mRNA levels were caused by changes in their stabilities. Although RBPs regulate the decay rates of multiple regulons, only 16% of all S. pombe mRNAs were affected in any of the 74 deletion strains. This suggests that other players or mechanisms are required to generate the observed range of RNA half-lives of a eukaryotic transcriptome.
dc.description.sponsorshipThis work was supported by a Biotechnology and Biological Sciences Research Council grant BB/J007153/1 to JM (http://www.bbsrc.ac.uk), a Masdar Institute fellowship to AH (http://www.masdar.ac.ae/) and a Herchel Smith Postdoctoral fellowship to CC (http://www.herchelsmith.cam.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.languageEnglishen
dc.language.isoenen
dc.publisherPLOS
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleSystematic analysis of the role of RNA-binding proteins in the regulation of RNA stabilityen
dc.typeArticle
dc.description.versionThis is the final published version. It first appeared at http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004684.en
prism.numbere1004684en
prism.publicationDate2014en
prism.publicationNamePLOS Geneticsen
prism.volume10en
dc.rioxxterms.funderBBSRC
dc.rioxxterms.projectidBB/J007153/1
dcterms.dateAccepted2014-08-18en
rioxxterms.versionofrecord10.1371/journal.pgen.1004684en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-11-06en
dc.contributor.orcidMata, Juan [0000-0002-5514-3653]
dc.identifier.eissn1553-7404
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/J007153/1)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales