环状RNA的生物学功能及其在疾病发生中的作用-李培飞

:ACTABIOPHYSICASINICAVol.30No.1Jan.2014:15-2315-23RNA3152112013-12-202014-01-20(81171660)(201301)(2012A610207)(2011B82014)(XKL11D2127)(0574)[e-mail]（circularRNA,circRNA）、RNARNA。，circRNA，。circRNARNA（microRNA,miRNA），miRNA，miRNA。circRNA、、，circRNA，。circRNA、。RNA；RNA；Q75DOI10.3724/SP.J.1260.2014.30171RNA(circularRNAcircRNA)、RNA。circRNA2070RNA[1,2]。1979HsuCoca-Prados[3]RNA。Arnberg[4]circRNA。1993circRNA[5]。circRNARNA[5]1999circRNA[6～13]。RNA(RNAsequencingRNA-seq)15ACTABIOPHYSICASINICA｜Vol.30No.1｜Jan.2014/MiniReview20143011circRNA(A)pre-mRNARNA。RNA。(B)。13'45'circRNA。(C)。13circRNA。(D)circRNA。ciRNAFig.1FormationofcircularRNA(A)Pre-mRNAisproceededtolinearRNAascommonlythought.Intronsarefirstlyremoved;thenexonsarealternativelyjointedtoformthelinearRNA.(B)Lariat-drivencircularization.Splicedonorin3'endofexon1andspliceacceptorin5'endofexon4arecovalentlyjointedtogether;thentheintronsareremoved;andfinallycircRNAisformed.(C)Intron-pairing-drivencircularization.Bybase-pairing,intron1andintron3areformedcircularstructure;thenintronsareremovedtoformcircRNA.(D)CircularintronicRNA.IntronitselfcircularizesandthenformscircRNA(ciRNA)Exon1Exon2Exon3Exon45'3'3'3'5'5'Exon2Exon2Exon3Exon3Exon3Exon2Exon4Exon1Exon4Exon1CannonicalexonskippingIntralariatsplicingcircRNAformationSpliceacceptorSplicedonor(B)Intron1Intron2Intron33'3'3'3'5'5'5'5'Exon1Exon1Exon1Exon1Exon2Exon2Exon2Exon3Exon3Exon3Exon4Exon4Exon4Exon4Intron1Intron2Intron3(A)3'3'3'3'3'5'5'5'5'5'Exon1Exon1Exon1Exon1Exon2Exon3Exon4Intron1Intron2Intron3Exon2Exon2Exon4Exon4Exon3Exon1Exon2Exon3Exon3(C)Exon2Exon2IntronciRNA(D)circRNA[14]。Jeck[15]25000circRNAMemczak[16]RNA-seq[14]1950circRNA、1903circRNA(81circRNA)724circRNA。circRNA、。circRNA、、。circRNAcircRNAmRNA(precursormessengerRNApre-mRNA)RNA(1A)16｜ACTABIOPHYSICASINICARNA/MiniReviewpre-mRNAcircRNA[14～17]。circRNAcircRNARNA(circularintronicRNA,ciRNA)[18,19]。RNARNAJeck[15](1B1C)circRNAZhang[20]circRNA(1D)。circRNA。circRNAcircRNA1)10[14,15]2)RNaseRRNA[15,16]3)[14,15][20]4)[20]5)6)circRNARNA(microRNAmiRNA)(microRNAresponseelementMRE)miRNA7)RNA(non-codingRNAncRNA)8)circRNA[20]。circRNAMemczak[16]circRNA。circRNAmiRNA1(antisensetothecerebellardegeneration-relatedprotein1transcriptCDR1as)Hansen[17]20111(cerebellardegeneration-relatedprotein1CDR1)(naturalantisensetranscriptNAT)。NATCDR1as70RNA-7(microRNA-7miR-7)MRERNA(RNA-inducedsilencingcomplexesRISC)[16,21]。miR-7miR-7[22]miRNA[15,16,21,23]。CDR1asmiR-7RNA(circularRNAspongeformiR-7CiRS-7)[21]。CDR1asmiR-7miR-7miR-7CDR1asmiR-7(2)。miRNARNA(competingendogenousRNAceRNA)[24]。Memczak[16]CDR1asmiR-7。Hansen[17]CDR1asmiR-7RISCmiR-671miR-67117ACTABIOPHYSICASINICA｜Vol.30No.1｜Jan.2014/MiniReview2014301Y(sex-determiningregionYSRY)。RNA。RNA[7,25]。SRYcircRNA[7,26,27]。Hentze[21]SRYCDR1ascircRNARNA-138(microRNA-138miR-138)16MREmiR-138miR-138miR-138。circRNAmiRNA[21]。circRNA(ciRNA)20%RNA[28]。RNA(smallnucleolarRNAsnoRNA)[29,30]、miRNA[31,32]ncRNA[18]。52(ankyrinrepeatdomain52ANKRD52)ciRNA(ciRNAderivedfromintronofANKRD52ci-ankrd52)[33,34]。Zhang[20](antisenseoligodeoxynucleotideASO)ci-ankrd52ankrd52mRNAankrd52。ciRNAmiRNAcircRNAmiRNAciRNA2CDR1asmiR-7(A)miR-7(B)miR-7Fig.2CDR1asindirectlyregulatetheexpressionofmiR-7'stargets(A)TheexpressionofmiR-7'stargetsisincreasedthroughrecruitinganumberofmiR-7byCDR1as;(B)CDR1asfunctionsasamiR-7buffertoinhibittheexpressionofsomeofmiR-7'stargets(A)(B)miR-7miR-7mRNAmRNAAAAAAAAAAAAAAAAAAAAAAAAACDR1asCDR1asCDR1asmiR-7。18｜ACTABIOPHYSICASINICARNA/MiniReview3circRNA(A)miRNAceRNA(B)(C)。IRESFig.3ThefunctionsofcircRNAs(A)ActingasamiRNAspongeorceRNA;(B)DirectlytargetingmRNAbypartlybasepairing;(C)Usedasthetemplateofproteinsynthesis.IRES:InternalribosomeentrysitemiRNAmiRNAmiRNAmiRNAmiRNAmiRNAmRNAlncRNAcircRNAmRNAAAAAAATranslationIREScircRNA(A)(B)(C)RNA[20]。circRNAcircRNAmiRNA(3)。circRNAcircRNA、、。INK4RNA(circularantisensenon-codingRNAintheINK4locuscANRIL)4(cyclin-dependentkinase4inhibitorCDK4aINK4a)(alterativereadingframeARF)(INK4A/ARF)[35]。cANRIL(singlenucleotidepolymorphismSNP)SNPcANRIL。cANRIL(polycombgroupPcG)INK4a/ARF[36]。2080CDR1[37～39]。20CDR1as[37]CDR1as[17]。miRNAmiR-7、[37]。CDR1as。———(N)CDR1as(S)[39]。19ACTABIOPHYSICASINICA｜Vol.30No.1｜Jan.2014/MiniReview2014301(prionproteinPrPC)HEK293CDR1as[40]PrPCCDR1as。CDR1as[22]。CDR1asmiRNAceRNAmiR-7miR-7CDR1asmiR-7(2)。miR-7α-(α-synuclein)。miR-7[41]。βmiR-7(mammaliantargetofrapamycinmTOR)[42]。miR-7β。miR-7(epidermalgrowthfactorreceptor,EGFR)、1(insulinreceptorsubstrate-1IRS-1)[43]、IRS-2、p21-1(p21-activatedkinase-1Pak1)[44]Raf1[45]。miR-7B-2(B-celllymphoma-2BCL-2)A549[46]。miR-7miR-7[49]。circRNA。。miRNAcircRNAmiRNAcircRNA。circRNA、RNA(RNA-bindingproteinRBP)[23]。circRNA。20｜ACTABIOPHYSICASINICARNA/MiniReview1.WiluszJE,SharpPA.Molecularbiology.AcircuitousroutetononcodingRNA.Science,2013,340(6131):440~4412.WuQ,WangY,CaoM,PantaleoV,BurgyanJ,LiWX,DingSW.Homology-independentdiscoveryofreplicatingpathogeniccircularRNAsbydeepsequencingandanewcomputationalalgorithm.ProcNatlAcadSciUS