Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm 英文参考文献.docVIP

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Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm 英文参考文献.doc

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Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm 英文参考文献

Genome-WideAssessmentofAU-RichElementsbythe AREScoreAlgorithm MilanSpasic1,CarolineC.Friedel2,JohannaSchott1,JochenKreth1,KathrinLeppek1,SarahHofmann1, SevimOzgur1,GeorgStoecklin1* 1Helmholtz Junior Research Group Posttranscriptional Control of Gene Expression, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany, 2InstituteforInformatics,Ludwig-Maximilians-Universita¨t (LMU)Mu¨nchen,Munich,Germany Abstract Inmammalian cells, AU-rich elements (AREs) arewell knownregulatory sequences located in the39 untranslated region (UTR)ofmanyshort-livedmRNAs.AREscausemRNAstobedegradedrapidlyandtherebysuppressgeneexpressionatthe posttranscriptionallevel.BasedonthenumberofAUUUApentamers,theirproximity,andsurroundingAU-richregions,we generated analgorithm termedAREScore thatidentifies AREs andprovides anumericalassessment of theirstrength. By analyzing the AREScore distribution in the transcriptomes of 14 metazoan species, we provide evidence that AREs were selectedforinseveralvertebratesandDrosophilamelanogaster.WethenmeasuredmRNAexpressionlevelsgenome-wide toaddresstheimportanceofAREsinSL2cellsderivedfromD.melanogasterhemocytes.Tis11,azincfingerRNA–binding protein homologous to mammalian tristetraprolin, was found to target ARE–containing reporter mRNAs for rapid degradationinSL2cells.DrosophilamRNAswhoseexpressioniselevateduponknockdownofTis11werefoundtohave higherAREScores.MoreoverhighAREScorescorrelatewithreducedmRNAexpressionlevelsonagenome-widescale.The precisemeasurementofdegradationratesfor26DrosophilamRNAsrevealedthattheAREScoreisaverygoodpredictorof short-livedmRNAs.Takentogether,thisstudyintroducesAREScoreasasimpletooltoidentifyARE–containingmRNAsand providescompellingevidencethatAREsarewidespreadregulatoryelementsinDrosophila. Citation: Spasic M, Friedel CC, Schott J, Kreth J, Leppek K, et al. (2012) Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm. PLoS Genet8(1):e1002433.doi:10.1371/journal.pgen.1002433 Editor:MichaelSnyder