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1、ResearchArticlesstepreaction(2,4–7).Thereac-Structuralbasisofpre-mRNAsplicingtionmechanismofpre-mRNAsplicingisthoughttocloselyre-semblethatofthegroupIIAorJingHang,*RuixueWan,*ChuangyeYan,*YigongShi†IIBself-splicingintron,eachin-MinistryofEducationKeyLaboratoryofProteinScience,Tsi
2、nghua-PekingJointCenterforLifeSciences,CenterforvolvingformationofanintronStructuralBiology,SchoolofLifeSciences,TsinghuaUniversity,Beijing100084,China.lariat,anddifferfromthatofthe*Theseauthorscontributedequallytothiswork.groupIICintron,whichsplices†Towhomcorrespondenceshouldbea
3、ddressed.E-mail:shi-lab@tsinghua.edu.cnbyhydrolysisthroughalinearintron(8,9).Aninvitrorecon-Splicingofpre-mRNAisperformedbythespliceosome.Inthecryo-EMstitutionofU2andU6snRNAsstructureoftheyeastspliceosome,U5snRNPactsasacentralscaffoldrevealedRNAsplicing-likeactiv-ontowhichU6andU2
4、snRNAsareintertwinedtoformacatalyticcenterityintheabsenceoftheproteinnexttoLoopIofU5snRNA.Magnesiumionsarecoordinatedbyconservedcomponents,stronglysupportingnucleotidesinU6snRNA.Theintronlariatisheldinplacethroughbasetheribozymehypothesis(10–13).pairinginteractionswithbothU2andU6
5、snRNAs,leavingthevariable-Buttheproteincomponentsoflengthmiddleportiononthesolvent-accessiblesurfaceofthecatalyticthespliceosomeareobviouslycenter.Theproteincomponentsofthespliceosomeanchorboth5′-and3′-indispensableforpre-mRNAendsoftheU2andU6snRNAsawayfromtheactivesite,directtheR
6、NAsplicingtoproceed,because,forsequences,andallowsufficientflexibilitybetweentheendsandtheexample,defectivesplicingduecatalyticcenter.Thus,thespliceosomeisinessenceaprotein-directedtomutatedRNAsequencecanberibozyme,withtheproteincomponentsessentialforthedeliveryofcriticalrescuedb
7、ymutationsinPrp8RNAmoleculesintocloseproximityofoneanotherattherighttimeforthefromS.cerevisiae(Spp42fromS.splicingreaction.onAugust22,2015pombe)(14–18).Whatarethefunctionsoftheproteincompo-Ineukaryoticcells,thecodingexonsinafreshlytran-nentsofthespliceosomeduringscribedprecursorm
8、essengerRNA(pre-mRNA)areinter-thetwo-ste
