Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus.docVIP

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Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus.doc

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Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus

BasePairingInteractionbetween59-and39-UTRs ControlsicaRmRNATranslationinStaphylococcus aureus IgorRuizdelosMozos1,MartaVergara-Irigaray1,VictorSegura2,MaiteVillanueva1,NereaBitarte1, MargaridaSaramago3,SusanaDomingues3,CeciliaM.Arraiano3,PierreFechter4,PascaleRomby4, JaioneValle1,CristinaSolano1,In?igoLasa1*,AlejandroToledo-Arana1* 1Laboratory ofMicrobialBiofilms.InstitutodeAgrobiotecnolog?′a(IDAB).UniversidadPu′blicadeNavarra-CSIC-GobiernodeNavarra.CampusdeArrosad?′a.Pamplona, Spain,2Genomics,ProteomicsandBioinformaticsUnit.CenterforAppliedMedicalResearch.UniversityofNavarra.Pamplona,Spain,3InstitutodeTecnologiaQu?′micae Biolo′gica,UniversidadeNovadeLisboa.Oeiras,Portugal,4ArchitectureetRe′activite′ del’ARN,Universite′ deStrasbourg,CNRS,IBMC.Strasbourg,France Abstract Thepresenceofregulatorysequencesinthe39untranslatedregion(39-UTR)ofeukaryoticmRNAscontrollingRNAstability and translation efficiency is widely recognized. In contrast, the relevance of 39-UTRs in bacterial mRNA functionality has beendisregarded.Here,wereportevidencesshowingthataroundone-thirdofthemappedmRNAsofthemajorhuman pathogenStaphylococcusaureuscarry39-UTRslongerthan100-ntandthus,potentialregulatoryfunctions.Weselectedthe long39-UTRoficaR,whichcodesfortherepressorofthemainexopolysaccharidiccompoundoftheS.aureusbiofilmmatrix, toevaluatetherolethat39-UTRsmayplayincontrollingmRNAexpression.Weshowedthatbasepairingbetweenthe39- UTRandtheShine-Dalgarno(SD)regionoficaRmRNAinterfereswiththetranslationinitiationcomplexandgeneratesa double-strandedsubstrateforRNaseIII.Deletionorsubstitutionofthemotif(UCCCCUG)withinicaR39-UTRwassufficientto abolish this interaction and resulted in the accumulation of IcaR repressor and inhibition of biofilm development. Our findings provide a singular example of anew potential post-transcriptional regulatory mechanism to modulate bacterial geneexpressionthroughtheinteractionofa39-UTRwiththe59-UTRofthesamemRNA. Citation:RuizdelosMozosI,Vergara-IrigarayM,SeguraV,Vill