Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model 英文参考文献.docVIP

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Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model 英文参考文献.doc

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Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model 英文参考文献

Genome-ScaleAnalysisofTranslationElongationwitha RibosomeFlowModel ShlomiReuveni1,2.,IsaacMeilijson1,MartinKupiec3,EytanRuppin4,5,TamirTuller6,7. * 1DepartmentofStatisticsandOperationsResearch,SchoolofMathematicalSciences,TelAvivUniversity,RamatAviv,Israel,2SchoolofChemistry,TelAvivUniversity, RamatAviv,Israel,3MolecularMicrobiologyandBiotechnology,TelAvivUniversity,RamatAviv,Israel,4SchoolofComputerSciences,TelAvivUniversity,RamatAviv, Israel, 5School of Medicine, Tel Aviv University, Ramat Aviv, Israel, 6Faculty of Mathematics and Computer Science, Weizmann Institute of Science, Rehovot, Israel, 7DepartmentofMolecularGenetics,WeizmannInstituteofScience,Rehovot,Israel Abstract Wedescribethefirstlargescaleanalysisofgenetranslationthatisbasedonamodelthattakesintoaccountthephysical anddynamical natureofthis process.The RibosomalFlowModel (RFM)predicts fundamentalfeatures ofthetranslation process, including translation rates, protein abundance levels, ribosomal densities and the relation between all these variables,betterthanalternative(‘non-physical’)approaches.Inaddition,weshowthattheRFMcanbeusedforaccurate inferenceofvariousotherquantitiesincludinggenes’initiationratesandtranslationcosts.Thesequantitiescouldnotbe inferredbypreviouspredictors.Wefindthatincreasingthenumberofavailableribosomes(orequivalentlytheinitiation rate)increasesthegenomictranslationrateandthemeanribosomedensityonlyuptoacertainpoint,beyondwhichboth saturate. Strikingly, assuming that the translation system is tuned to work at the pre-saturation point maximizes the predictive power of the model with respect to experimental data. This result suggests that in all organisms that were analyzed(frombacteriatoHuman),theglobalinitiationrateisoptimizedtoattainthepre-saturationpoint.Thefactthat similarresultswerenotobservedforheterologousgenesindicatesthatthisfeatureisunderselection.Remarkably,thegap between the performance of the RFM and alternative predictors is strikingly large in the case of hetero