LongNoncodingRNAs:Genomics,Functions,Methodologies,ModesofActionsWeiGuifeng,guifengwei@gmail.comInstituteofBiophysics,ChineseAcademyofSciencesRNABiology1941OneGene,OneEnzyme1953DNA,doublehelix1958Crick,CentralDogma1961mRNAdiscoveryJacob&MonodLacModel1966hnRNA1977Introndiscovery1989RNaseP1990H19lncRNA1991XIST1993lin-4miRNA1998RNAi1999TSIXSmallRNAsinPTGSBefore20002000microRNAs25/1/272After20002001DicerinRNAiRNAinepigeneticregulation2002ManyncRNAsAIRinimprinting2003Drosha2004AGO22005piRNAsDiscoveryoftheCRISPRsystemofbacterialRNA-baseddefense2007HOTAIR2009ChromatinstateandlincRNA2010EnhancerRNA2012ENCODECRISPR/Cas9RNAmodification20132014CircularRNARNABiology25/1/273TheENCODEProjectConsortium.Nature2012ENCODEProjectYueFengetal.Nature2014LongNoncodingRNAsENCODEProjectExtensivetranscriptionhttp://www.gencodegenes.org/GenomicsIgorUlitskyetal.Cell2013LongNoncodingRNAsIgorUlitskyetal.Cell2013LongNoncodingRNAsLongNoncodingRNAsGenomicsOtherformsoflncRNAs:sno-lncRNA,CircularRNALongNoncodingRNAsFaticaetal.NAT.REV.GENETICS2014InCis-orTransLongNoncodingRNAsFaticaetal.NAT.REV.GENETICS2014InCis-orTransLongNoncodingRNAsLowabundanceTissue-specificityMoranCabilietal.Genes&Dev.2011Stemcellself-renewalanddifferentiation;DevelopmentandLineagecommitment;Immunology;Neurogenetics;Cancerprogression(TumorSuppressororOncogene);……LongNoncodingRNAsHistonemodification(HOTAIR),DNAmethylation,high-orderchromatinstructure(Firre),transcriptionfactorbindingactivity(RMSTwithSOX2),decoymodel(PANDA),……LongNoncodingRNAsHOTAIRaffectsexpressionoftheHOXDgenefamily;XISTiscrucialfortheXchromosomeinactivation;lincRNA-RORaffectsreprogrammingefficiency;AiriscrucialforimprintingcontrolatIgf2rlocus;NRONaffectsNFATtranscriptionfactoractivity;Tug1affectsretinadevelopmentthroughtheregulationofthecellcycle;HOTTIPactivatestheexpressionofHOXAgenefamilythroughphysicallyinteractingwithWDR5;……Severalwell-characterizedlncRNAswithdetailedmolecularmechanismsLongNoncodingRNAs>=30%oflincRNAsphysicallyinteractwithchromatinregulatoryproteins.MitchellGuttmanetal.Nature2011FourprinciplesofnucleicacidandproteininteractionsceRNA(miRNAsponge)Guttman&Rinn.Nature2012LongNoncodingRNAsThankyou