ArticleANetworkofNoncodingRegulatoryRNAsActsintheMammalianBrainGraphicalAbstractHighlightsdAlongnoncodingRNA,acircularRNA,andtwomicroRNAsformaregulatorynetworkdTheCyranolongnoncodingRNAdirectspotent,multiple-turnoverdestructionofmiR-7dUncheckedmiR-7preventsaccumulationofCdr1ascircularRNAincytoplasmofneuronsdmiR-7preventsthisaccumulationbyenhancingthemiR-671–directedslicingofCdr1asAuthorsBenjaminKleaveland,CharlieY.Shi,JoannaStefano,DavidP.BartelCorrespondencedbartel@wi.mit.eduInBriefThreedifferentclassesofnoncodingRNAconvergeinaregulatorynetworkwherebyalongnoncodingRNArepressesamicroRNAviatarget-directedmicroRNAdegradation,whichinturnenablestheaccumulationofacircularRNAinthemousebrain.Kleavelandetal.,2018,Cell174,350–362July12,2018ª2018ElsevierInc.https://doi.org/10.1016/j.cell.2018.05.022ArticleANetworkofNoncodingRegulatoryRNAsActsintheMammalianBrainBenjaminKleaveland,1,2,3,4CharlieY.Shi,1,2,3JoannaStefano,1,2,3andDavidP.Bartel1,2,3,5,*1HowardHughesMedicalInstitute,Cambridge,MA02142,USA2WhiteheadInstituteofBiomedicalResearch,Cambridge,MA02142,USA3DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,MA02139,USA4DepartmentofPathology,MassachusettsGeneralHospital,Boston,MA,02114,USA5LeadContact*Correspondence:dbartel@wi.mit.eduhttps://doi.org/10.1016/j.cell.2018.05.022SUMMARYNoncodingRNAs(ncRNAs)playincreasinglyappre-ciatedgene-regulatoryroles.Here,wedescribearegulatorynetworkcenteredonfourncRNAs—alongncRNA,acircularRNA,andtwomicroRNAs—usinggeneeditinginmicetoprobethemolecularconsequencesofdisruptingkeycomponentsofthisnetwork.ThelongncRNACyranousesanexten-sivelypairedsitetomiR-7totriggerdestructionofthismicroRNA.Cyrano-directedmiR-7degradationismuchmoreeffectivethanpreviouslydescribedex-amplesoftarget-directedmicroRNAdegradation,whichcomeprimarilyfromstudiesofartificialandviralRNAs.ByreducingmiR-7levels,Cyranopre-ventsrepressionofmiR-7–targetedmRNAsanden-ablesaccumulationofCdr1as,acircularRNAknowntoregulateneuronalactivity.WithoutCyrano,excessmiR-...
