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《PNAS-2013-Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、HumaneIF4EpromotesmRNArestructuringbystimulatingeIF4Ahelicaseactivity1KaterynaFeoktistova,EnkheeTuvshintogs,AngelieDo,andChristopherS.FraserDepartmentofMolecularandCellBiology,CollegeofBiologicalSciences,UniversityofCalifornia,Davis,CA95616Edited*byJenniferA.Doudna,UniversityofCali
2、fornia,Berkeley,CA,andapprovedJuly5,2013(receivedforreviewFebruary27,2013)Elevatedeukaryoticinitiationfactor4E(eIF4E)levelsfrequentlyUnwindingofsecondarystructureinthemRNA5′-UTRoccurinavarietyofhumancancers.OverexpressionofeIF4Epro-involvestheactivityoftheeIF4AhelicasecomponentofeI
3、F4Fmotescellulartransformationbyselectivelyincreasingthetrans-(13,14).HumaneIF4AfunctionsasanRNA-dependentATPaselationofproliferativeandprosurvivalmRNAs.ThesemRNAspossessthatbidirectionallyunwindsRNAduplexes(15–17).Consistenthighlystructured5′-UTRsthatimpederibosomerecruitmentandwi
4、thotherDEAD-boxproteins,strandseparationispromotedscanning,yetthemechanismforhoweIF4Eabundanceelevatesthroughwell-definedconformationalrearrangementsofitsRecAtheirtranslationisnoteasilyexplainedbyitscap-bindingactivity.homologydomains(18–20).AlthougheIF4AisarelativelypoorHere,weshow
5、thateIF4Epossessesanunexpectedsecondfunctionhelicaseonitsown,itsATPaseandduplexunwindingactivitiesintranslationinitiationbystronglystimulatingeukaryoticinitiationarestimulatedbyeIF4Gandthehelicaseaccessoryprotein,factor4A(eIF4A)helicaseactivity.Importantly,wedemonstrateeIF4B(15,17,
6、21–24).Inaddition,theinteractionofthepoly(A)thatthisactivitypromotesmRNArestructuringinamannerthatbindingprotein(PABP)witheIF4GalsostimulatestheATPaseisindependentofitscap-bindingfunction.Toexplainthesefind-andduplexunwindingactivityofeIF4A(25).Despitethefactings,weshowthattheeIF4E-
7、bindingsiteineukaryoticinitiationthatanincreaseineIF4Eavailabilitystimulatestherateoffactor4G(eIF4G)functionsasanautoinhibitorydomaintomodu-translationinitiationonhighlystructuredmRNAs,noevidencelateitsabilitytostimulateeIF4Ahelicaseactivity.BindingofeIF4Eexiststolinkthepresenceofe
8、IF4EintheeIF4Fcomplexwithc
