Posttranscriptional Expression Regulation What Determines Translation Rates 英文参考文献.docVIP

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Posttranscriptional Expression Regulation What Determines Translation Rates 英文参考文献.doc

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Posttranscriptional Expression Regulation What Determines Translation Rates 英文参考文献

PosttranscriptionalExpressionRegulation: WhatDeterminesTranslationRates? Regina Brockmann1,2[,Andreas Beyer1,3[,Ju¨rgen J.Heinisch2,Thomas Wilhelm1* 1TheoreticalSystemsBiology,LeibnizInstituteforAgeResearch,FritzLipmannInstitute,Jena,Germany,2FachbereichBiologie/Chemie,AGGenetik,Universita¨tOsnabru¨ck, Osnabru¨ck,Germany,3DepartmentofBioengineering,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Recentanalysesindicatethatdifferencesinproteinconcentrationsareonly20%–40%attributabletovariablemRNA levels,underliningtheimportanceofposttranscriptionalregulation.Generally,proteinconcentrationsdependonthe translation rate (which is proportional to the translational activity, TA) and the degradation rate. By integrating 12 publiclyavailablelarge-scaledatasetsandadditionaldatabaseinformationoftheyeastSaccharomycescerevisiae,we systematicallyanalyzedfivefactorscontributingtoTA:mRNAconcentration,ribosomedensity,ribosomeoccupancy, the codon adaptation index, and a newly developed ‘‘tRNA adaptation index.’’ Our analysis of the functional relationship between the TA and measured protein concentrations suggests that the TA follows Michaelis–Menten kinetics.ThecalculatedTA,togetherwithmeasuredproteinconcentrations,allowedustoestimatedegradationrates for 4,125 proteins under standard conditions. A significant correlation to recently published degradation rates supports our approach. Moreover, based on a newly developed scoring system, we identified and analyzed genes subjectedtotheposttranscriptionalregulationmechanism,translationondemand.Nextweappliedthesefindingsto publicly available data of protein and mRNA concentrations under four stress conditions. The integration of these measurementsallowedustocomparethecondition-specificresponsesattheposttranscriptionallevel.Ouranalysisof all62proteinsthathavebeenmeasuredunderallfourconditionsrevealedproteinswithveryspecificposttranscrip- tional stress response, in contrast to more generic responders, which were