RESEARCHHIGHLIGHTAcirculartwistonmicroRNAregulationCellResearch(2017)27:1401-1402.doi:10.1038/cr.2017.136;publishedonline31October2017CellResearch(2017)27:1401-1402.©2017IBCB,SIBS,CASAllrightsreserved1001-0602/17$32.00www.nature.com/crCircularRNAs(circRNAs)areanovelclassofRNAwhosephysiologi-calfunctionhasyettobeinvestigated.ArecentpublicationinSciencepro-videsthefirstevidenceofthebio-logicalrelevanceofacircRNAinaninvivomodelandunveilsanunexpectedtwistontheircrosstalkwithmiRNAs.In1993,Cocquerelleetal.[1],in-spiredbythediscoveryofscrambledexons,investigatedtheexistenceoftwononpolyadenylatedcircularRNA(circRNA)isoformsgeneratedfromtheets-1locusinhumancells.Inaconcur-rentstudy,Capeletal.[2]identifiedacircRNAarisingfromtheSrylocus.Twodecadeslater,tremendousadvancesinRNAsequencingtechnologiesandbioinformaticanalysisallowedthreegroupstovalidatethedataofCocque-relleandCapel[3-6].SofarthousandsofcircRNAshavebeenuncovered.Theyappeartobegeneratedastheproductofaproactiveformofbacksplicingofpre-mRNAs.PotentialmechanismsofactionhavebeeninvestigatedforanumberofcircRNAs.Thevastmajorityappeartobenon-codingRNAsthatplayaroleintranscriptionalandtranslationalregula-tion,similartothebetter-characterizedlongnon-codingRNAs(lncRNAs).TheroleofcircRNAsas“miRNA-sponges”hasarguablybeenextensivelyexplored.miRNAsareshortregulatoryRNAsthatrecognizetargetRNAsthroughtheirbindingsites(miRNArecognitionelements,MRE)andcannegativelyme-diatetheirabundanceandtranslationalpotential.Afewyearsago,ourgroupproposedacompetingendogenousRNA(ceRNA)hypothesis[7],inwhichdifferentRNAscancommunicatewithandregulateeachotherbycompetingformiRNAsthroughMREs.Thismodelimpliesintricatecrosstalkbywhichthemodula-tionofaRNAwithmultipleMREsforspecificmiRNAsresultsintheconcomi-tantregulationofothertargetsofthesemiRNAs.Thishypothesiswassubse-quentlyvalidatedforbothcodingandnon-codinglinearRNAsbyourgroupandothers.TheRajewskyandKjemslaboratoriesfocusedonacircRNA,Cdr1as,anditsceRNAactivity[4,6].Specificallyexpressedinthemammali...
