Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae 英文参考文献.docVIP

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Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae 英文参考文献.doc

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Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae 英文参考文献

Freebergetal.GenomeBiology2013,14:R13 /content/14/2/R13 RESEARCH OpenAccess Pervasiveanddynamicproteinbindingsitesof themRNAtranscriptomeinSaccharomyces cerevisiae MalloryAFreeberg1,2?,TingHan1,3?,JamesJMoresco4,AndyKong1,2,Yu-ChengYang5,ZhiJohnLu5, JohnRYatesandJohnKKim1* Abstract Background:Protein-RNAinteractionsareintegralcomponentsofnearlyeveryaspectofbiology,including regulationofgeneexpression,assemblyofcellulararchitectures,andpathogenesisofhumandiseases.However, studiesinthepastfewdecadeshaveonlyuncoveredasmallfractionofthevastlandscapeoftheprotein-RNA interactomeinanyorganism,andevenlessisknownaboutthedynamicsofprotein-RNAinteractionsunder changingdevelopmentalandenvironmentalconditions. Results:Here,wedescribethegPAR-CLIP(globalphotoactivatable-ribonucleoside-enhancedcrosslinkingand immunopurification)approachforcapturingregionsoftheuntranslated,polyadenylatedtranscriptomeboundby RNA-bindingproteins(RBPs)inbuddingyeast.Wereportover13,000RBPcrosslinkingsitesinuntranslatedregions (UTRs)covering72%ofprotein-codingtranscriptsencodedinthegenome,confirming3’UTRsasmajorsitesfor RBPinteraction.ComparativegenomicanalysesrevealthatRBPcrosslinkingsitesarehighlyconserved,andRNA foldingpredictionsindicatethatsecondarystructuralelementsareconstrainedbyproteinbindingandmayserve asgeneralizablemodesofRNArecognition.Finally,38%of3’UTRcrosslinkingsitesshowchangesinRBP occupancyuponglucoseornitrogendeprivation,withmajorimpactsonmetabolicpathwaysaswellas mitochondrialandribosomalgeneexpression. Conclusions:Ourstudyoffersanunprecedentedviewofthepervasivenessanddynamicsofprotein-RNA interactionsinvivo. Background also reversibly aggregate into granules to allow RNA A diverse and expanding repertoire of RNA-binding storage and decay in response to stimuli [7,8]. These proteins(RBPs)ensuresfaithfulexpressionandfunction andmanyotherprocesses aredriven bylarge, complex ofsubstratemRNAs[1-3].ManyRNAsareorganizedby networksofprotein-RNAinteractionsthatprovidespe- RBPs