王艳丽研究员
YanliWang,Professor

专家类别:百人计划，研究员
简历&研究组工作摘要：2002－2004中国科学技术大学博士2005—2006中国科学院生物物理研究所助理研究员2006－2010美国斯隆-凯瑟琳癌症研究中心博士后、副研究员、高级研究员2010—至今中国科学院生物物理研究所“百人计划”研究员目前本课题组主要集中在RNA干扰（RNAinterference，RNA）相关蛋白的结构与功能研究。RNAi是指在进化过程中高度保守的、由双链RNA介导的特异性基因沉默现象。Argonaute蛋白是RNA基因沉默途径中核心元件，其PIWI结构域能够催化引导链介导的mRNA的特异性降解。我们解析了argonaute蛋白与引导链的二体复合物的晶体结构，观察到了引导链的结合通道及复合物形成过程中蛋白构象变化，阐明了引导链识别靶RNA的分子机制；随后我们解析了一系列的argonaute蛋白结合引导链及靶RNA的三体复合物的晶体结构，第一次观察到靶链与引导链在argonaute蛋白中的结合方式，进一步阐明了引导链与靶RNA互补配对形成双链，以及此双链的延伸过程中蛋白与引导链所发生的显著构象变化；我们还通过解析三体复合物的晶体结构阐明了在Mg2+辅助下argonaute蛋白特异性切割靶RNA的分子机制。上述结果详细解释了argonaute沉默复合体参与调控基因沉默的具体途径和方式，阐明了其如何选择并切割RNA分子，最终降解RNA分子使基因沉默的过程。
Biography&Introduction：2002—2004Ph.DUniversityofScienceandTechnologyofChina2005—2006ResearchAssistantInstituteofBiophysics,ChineseAcademyofSciences2006—2010ResearchFellow,ResearchAssociate,andSeniorResearchScientistMemorialSloan-KetteringCancerCenter,NewYork2010-presentProfessorInstituteofBiophysics,ChineseAcademyofSciencesOurresearchinterestsfocusonthestructureandfunctionoftheargonautesilencingcomplex,whichiscloselylinkedtotheRNAinterference（RNAi）.RNAiisthehighlyconservativeprocessintheevolutionaryandreferstotheinhibitionofgeneexpressionbysmalldouble-strandedRNAmolecules.Theargonaute(Ago)protein,asakeycatalyticcomponentoftheRNA-inducedsilencingcomplex,hasacentralroleintheRNAinterferencepathwaybymediatingthematurationofsmallinterferingRNA(siRNA)throughinitialdegradationofthepassengerstrand,followedbyguide-strand-mediatedsequence-specificcleavageoftargetmRNA.WereportedonthecrystalstructureofThermusthermophilusargonauteboundtoaDNAguidestrand,therebyidentifyingthenucleic-acid-bindingchannelpositionedbetweenthePAZ-andPIWI-containinglobes,aswellasthepivot-likeconformationalchangesassociatedwithcomplexformation.WealsothrowlightonthemolecularmechanismintheguidestranddistinguishingthetargetRNA.ThenwereportonstructuresofternarycomplexesofAgocatalyticmutantswithguideDNAandcomplementarytargetRNAsofvariouslengths,whichdefinethemolecularbasisforMg²⁺-facilitatedsite-specificcleavageofthetarget.Weobservedpivot-likedomainmovementswithintheAgoscaffoldonproceedingfromnucleationtopropagationstepsofguide–targetduplexformation,withduplexzipperingbeyondoneturnofthehelixrequiringthereleaseofthe3′-endoftheguidefromthePAZpocket.TheseresultsshowedhowtheargonautesequencespecificallycleavestargetmRNAandregulatesthegenesilencingbymRNAdegradation.
SelectedPublications：1.RüdelS,WangY,LenobelR,K?rnerR,HsiaoHH,UrlaubH,PatelD,MeisterG.PhosphorylationofhumanArgonauteproteinsaffectssmallRNAbinding.NucleicAcidsRes.2011,39:2330-43.2.WangY.,LudwigJ.,SchuberthC.,GoldeckM.,SchleeM.,LiH.,JuranekS.,ShengG.,MicuraR.,TuschlT.,HartmannG.,PatelD.,Structuralandfunctionalinsightsinto5'-pppRNApatternrecognitionbytheinnateimmunereceptorRIG-I.NatStructMolBiol.2010,17:781-7..2010,17:781-7.3.WangY,JuranekS,LiH,ShengG,TuschlT,PatelDJ.Nucleation,propagationandcleavageoftargetRNAsinAgosilencingcomplexes.Nature.2009,461:754-761.4.WangY,JuranekS,LiH,ShengG,TuschlT,PatelDJ.Structureofanargonautesilencingcomplexwithaseed-containingguideDNAandtargetRNAduplex.Nature.2008,456:921-926.5.WangY,ShengG,JuranekS,TuschlT,PatelDJ.,Structureoftheguide-strand-containingargonautesilencingcomplex.Nature.2008,456:209-213.6.WangY,LiuL,WeiZ,ChengZ,LinY,GongW.Seeingtheprocessofhistidinephosphorylationinhumanbisphosphoglyceratemutase.JBiolChem.2006,281:39642-8.7.WangY,WeiZ,LiuL,ChengZ,LinY,JiF,GongW.CrystalstructureofhumanBtypephosphoglyceratemutaseboundwithcitrate.Biochem.Biophys.Res.Commun.2005,331:1207-15.8.WangY,WeiZ,BianQ,ChengZ,WanM,LiuL,GongW，Crystalstructureofhumanbisphosphoglyceratemutase,J.Biol.Chem.2004,279:39132-8
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