Processivity and Coupling in Messenger RNA Transcription 英文参考文献.docVIP

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Processivity and Coupling in Messenger RNA Transcription 英文参考文献.doc

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Processivity and Coupling in Messenger RNA Transcription 英文参考文献

ProcessivityandCouplinginMessengerRNA Transcription StuartAitken1*,Marie-Ce′cileRobert2,RossD.Alexander1,3,IgorGoryanin1,EdouardBertrand2,JeanD. Beggs1,3 1Centre forSystems Biology,UniversityofEdinburgh, Edinburgh, UnitedKingdom,2InstitutdeGe′ne′tique Mole′culaire deMontpellier-CNRS UMR5535, Montpellier, France,3WellcomeTrustCentreforCellBiology,UniversityofEdinburgh,Edinburgh,UnitedKingdom Abstract Background:ThecomplexityofmessengerRNAprocessingisnowbeinguncoveredbyexperimentaltechniquesthatare capableofdetectingindividualcopiesofmRNAincells,andbyquantitativereal-timeobservationsthatrevealthekinetics. ThisprocessingiscommonlymodelledbypermittingmRNAtobetranscribedonlywhenthepromoterisintheonstate.In thissimpleon/offmodel,themanyprocessesinvolvedinactivetranscriptionarerepresentedbyasinglereaction.These processesincludeelongation,whichhasaminimumtimeforcompletionandprocessingthatisnotcapturedinthemodel. Methodology:Inthispaper,weexploretheimpactonthemRNAdistributionofrepresentingtheelongationprocessin moredetail.Considerationofthemechanismsofelongationleadstotwoalternativemodelsofthecouplingbetweenthe elongatingpolymeraseandthestateofthepromoter:Processivityallowspolymerasestocompleteelongationirrespective of the promoter state, whereas coupling requires the promoter to be active to produce a full-length transcript. We demonstratethatthesealternativeshaveasignificantimpactonthepredicteddistributions.Modelsaresimulatedbythe Gillespiealgorithm,andthethirdandfourthmomentsoftheresultingdistributionarecomputedinordertocharacterise the length of the tail, and sharpness of the peak. By this methodology, we show that the moments provide a concise summaryofthedistribution,showingstatistically-significantdifferencesacrossmuchofthefeasibleparameterrange. Conclusions: We conclude that processivity is not fully consistent with the on/off model unless the probability of successfully completing elongation is low—as has been observed. The results also suggest that some form