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ID:39301829
大小:789.01 KB
页数:40页
时间:2019-06-30
《关于真核生物降解及代谢过程的计算机模拟》由会员上传分享,免费在线阅读,更多相关内容在教育资源-天天文库。
1、关于真核生物mRNA降解及代谢过程的计算机模拟曹丹亚力桑那大学分子细胞生物学系DanCaoandRoyParkerHowardHughesMedicalInstitute&DepartmentofMolecularCellularBiologyUniversityofArizonaComputationalmodelingofmRNAturnoverDNAmRNAProteinTranscription,Splicing,transport…translationdegradationdegradationTheCentra
2、lDogmaWhywanttomodelthisprocess?1.IntegrationWhywanttomodelthisprocess(Cont’d)?Anexplanatory/descriptivetool1)correctionofmisconceptions2)helpinterpretresultcorrectly3)advicesuitableexperimentPredictionfromdiscrepanciesbetweensimulationresultandexperimentalresultAn
3、idealsystemtostartknowledge-drivensimulationPlentyofdataavailabletoestimatetheratesfordistinctsteps,includingsteadystatedistribution,half-lives,effectsofvariousmutants…MajorassumptionsTranscriptionisazerothorderprocess,allotherstepsarefirstorderprocessesAllstepsare
4、irreversibleNofeedbackloopsratesforallstepsSteadystatelevelofeachintermediatekineticsovercertainexperimentaltimecourseVirtualnortherngelfordirectcomparisonCybermRNATranscriptionalshut-offexp.(decayfromsteadystate)Transcriptionalpulsechaseexp.AtsteadystateInhibittra
5、nscriptionAttheendofashort“pulse”InhibittranscriptionAsamplescreenshotinputDeterminethefitnessofthemodelwiththeinvivodecaynetwork:MFA2pG&PGK1pGTheyrepresentaunstable(MFA2)andstable(PGK1)mRNAinyeastTheirdegradationhasbeenextensivelycharacterized,withlotsofdataavaila
6、bletoestimatetherates.E.g:transcriptionalpulsechasegelcangiveinformationfortheratesofdeadenylationanddecapping.Strongpoly(G)structureatthe3’UTRcantrapthedecayintermediates,giveadditionalinformationaboutinvivoprocess.E.g:ratesofterminaldeadenylationand3’to5’decayCom
7、parisonofmodelingresultswithexperimentalobservationsThesimulatedsteadystatepoly(A)distribution,pulsechasegelpattern,previouslycharacterizedmutants(transport,decapping,3’to5’decay…)arealsoconsistentwithexp.observations.ModelingofMFA2pGintranscriptionalpulsechaseObse
8、rvedComputedModelingofPGK1pGintranscriptionalpulsechaseObservedComputedThefactthatwecanreproducetheexperimentalresultsbymodelingsuggeststhatourmo
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