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MolecularMolecularⅣ.真核生物 轉錄及其調(diào)七、RNA加工(RNAmRNA加帽、加RNA編rRNA加tRNA加加帽 Cap3加帽 Cap3種主要的Cap1:1個2’-O-甲基核苷酸(真核細胞 Cap2:2個2’-O-甲基核苷酸(只在真核Cap0:無2’-O-甲基核苷酸(只在一些43種主要的5加帽 Cap不常見的WIREsRNA201016加帽 Cap不常見的WIREsRNA201017加帽 Cap不常見的WIREsRNA201018加帽 Cap磷酸的來來源于 來源于第一個核苷9加帽 Cap&RNA三磷酸酯鳥苷酸轉腺苷甲硫甲基轉移加帽 Cap聚腺苷酸化pre-mRNA3’長度:~200-250poly(A)polymerase把AMP殘基逐聚腺苷酸化Mechanismof聚腺苷酸化Mechanismof需各種蛋白因子輔聚腺苷酸化Polyadenylationpoly(A)位點上游約20nt處的poly(A)位點富GU區(qū)及富U3.帽子結構與poly(A)的功 ProtectmRNAsfromEnhancetranslatabilityofTransportofmRNAsoutofEfficiencyofsplicingTheeffectsoftheCapandpoly(A)onStabilityandTranslatabilityofmRNADanielR.Gallie, Fig.制制結TheeffectsoftheCapon出

不出也具的也具的不出作出 mRNAAllthreemRNA-ProcessingeventsOccursDuringTranscriptionSplicingbeginswhentranscriptionisstill occurswhen5’-endofRNAfirstemergesfrompolymerase;Polyadenylationoccurswhenthestill-growingmRNAiscutatthepolyadenylationsite.TheEffectsoftheCapandpoly(A)onpre-mRNASplicingpoly(A)能促進最后一個內(nèi)含子的接,而對其他內(nèi)含子的剪接無甚影響TheEffectsoftheCaponSplicing(firstintron)

Kyoto4.4.RNAEditing(RNA編輯些轉錄產(chǎn)生的mRNA與其編碼DNA細胞色素氧化酶II(cytochromeoxidaseII,細胞色素氧化細胞色素氧化酶III(cytochromeoxidaseIII,407UMPsaddedbyediting19encodedUMPsdeleted錐蟲RNAUGuide

哺乳動物RNA脫氨基化 Thelifecycleof.轉錄 ForTranslationalpoly(A)urnver細胞質(zhì)中,poly(A)因RNase的作用不斷變短, 發(fā)生,聚腺苷酸化信號為AAUAAA和上游7nt的(cytoplasmicpolyadenylationelement,DestabilizationofDestabilizationofTfR順烏頭酸脫輔基蛋鐵離子應答元件TfR:轉鐵蛋白Post-transcriptionalGene1.1.RNATheDiscoveryof1988,Gene-specificinhibitionbyanti-sense1990,SenseRNAshaveSimilarEffect(Rich1995,eitherSenseorAntisensearesufficienttocauseinterferenceinC.elegans(Guo&Kemphues).DiscoveryDiscoveryofRNANature(1998)391:806-Double-strandedC.

A,CK-,uninjected;B,Ck+,senseRNA;C,AntisenseRNA;D,dsRNAConclusion:dsRNAreducedmex-3betterthanantisenseDicercleavesdsRNAsinto22ntguide

起作用的莫非是這些小Nature.2001409:363-合成的小RNAs是否可起作用21nt22nt3’21-ntsiRNAduplexesspecificallysuppressexpressionofheterologousgenesinmammaliancelllines.Nature.2001May24;411:494-21-ntsiRNAduplexesspecificallysuppressexpressionofendogenousgenesinmammaliancelllines.Nature.2001May24;411:494-GreatSignificanceSmallinterferingRNA(siRNA)isaneasiertooltosilenceagenewithouttheneedtochangeitssequence,thuswillbeapowerfulweaponintherapyhumandisease.我怎么就沒想到呢Su2.2.AnotherfamilysmallAendogenoussmallRNA---Lin-lin-14VictorR.

Caenorhabditis.

lin-4Lin-4andoneof Cell75(5):843-2001,threelabsfound96newsmallRNAsinC.elegans,M.Drosophila,andhumancellHeLa,whichareendogenoussingle-strandedRNAsof21~23nt.TheynamedthemMicroRNAs.Thomas David VictorDepartmentofCellularBiochemistry,MaxPlanckInstituteforBiophysical

WhiteheadInstituteforBiomedicalResearch,and

DartmouthMedicalSchool,DepartmentofGenetics,USA.inRockefeller

ScienceVol294,853-864,TheTheCharacteristicofFeaturesFeaturesofthelin-4/let-7classMatureRNAof~22ntinLocationinintergenicorintronicHighlyconservedbetweencloserelatedProcessedfromastem-loopprecursortranscriptof~65nt.ScienceVol294,853-864,FromFrom2001to2005,alargenumberofmicroRNAswereidentifiedfromvariousmulti-cellularorganisms.3406miRNAsidentifiedtillNov13,ApproachestomiRNAgene

ApartofmiRshadbeen+- +- +-Drosophilamelanogaster +- +-Caenorhabditiselegans +- +- +-Xenopuslaevis +- +-Gallusgallus +- +- +-Gorillagorilla +-Homosapiens +- +-Musmusculus +-Rattusnorvegicus +- +-Daniorerio+- +-Arabidopsisthaliana +-OryzasativaNature431(7006):350-

+-Epstein +-Human microRNAsshareasimilarmechanismwithNat.Rev.Genet.5(7):522-4.The4.TheFunctionofEmbryonicProliferation&…

miR-1regulatethebalancebetweencellproliferationanddifferentiationthroughregulationofHand2.Hand2proteinHand2mRNATransversesectionsofwild-typeβ-MHC-miR-1transgenicheartsatE13.5showover-expressionofmiR-1ledtothin-walledventriclesandheartfailure.Tg:β-MHC-miR-1Nature436(7048):214-MicroRNAsControlPlantShapeAndArabidopsiswithmiR-jawmutationhaveserratedleavesNature425(6955):257-ArabidopsiswithAPETALA2mutation(miR- )havenumerousOverexpressionAPETALA2ledtolargeandmorestamensthanthewildwild Science303(5666):2022-MiRNAsMiRNAscontrolchemosensoryK,GeneregulatorycascadeinASELandGeneregulatorycascadeinASELandgcyguanylylcyclasereceptorgenesMiRNA-122regulateshepatocytedifferentiationduringliverdevelopmentAmodeformiRNAs'functioninstemcellstemcellcell-typemiRNAsmaycontrolthewhole processswitchingoffsomekeygenesinsuitableGlobalGlobaldown-regulationofmiRNAsin129outof217miRNAhadlowerexpressionlevelsintumourscomparedwithnormaltissues.high(red)lowNature435(7043):834-AmicroRNApolycistronasapotentialThelevelofmir-17-92pri-miRNAwasdeterminedby tativePCRin46lymphomas.

Overexpressionofthemir-17–19bclusteracceleratesc-myc-inducedlymphomagenesisinmice.Nature435(7043):828-AmodelformiRNAinvolvedinOverexpressionofmiRNAs-decreaseexpressionoftumorsuppressorUnderexpressionofmiRNAs-increasedexpressionof2010-9-VariousVariousNoncodingRNALength/size:~20-30micr

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