MolecularCellShortArticleRegulationofpri-miRNAProcessingbyaLongNoncodingRNATranscribedfromanUltraconservedRegionJuliaLiz,1AnnaPortela,1MartaSoler,1AntonioGo´mez,1HuiLing,2GracjanMichlewski,3GeorgeA.Calin,2So`niaGuil,1,*andManelEsteller1,4,5,*1CancerEpigeneticsandBiologyProgram(PEBC),BellvitgeBiomedicalResearchInstitute(IDIBELL),L’Hospitalet,08908Barcelona,Catalonia,Spain2ExperimentalTherapeutics&CancerGenetics,MDAndersonCancerCenter,TexasStateUniversity,Houston,TX77030,USA3WellcomeTrustCentreforCellBiology,UniversityofEdinburgh,King’sBuildings,Edinburgh,EH93JR,UK4SchoolofMedicine,DepartmentofPhysiologicalSciencesII,UniversityofBarcelona,08036Barcelona,Catalonia,Spain5InstitucioCatalanadeRecercaiEstudisAvanc¸ats(ICREA),08010Barcelona,Catalonia,Spain*Correspondence:sguil@idibell.cat(S.G.),mesteller@idibell.cat(M.E.)http://dx.doi.org/10.1016/j.molcel.2014.05.005SUMMARYNoncodingRNAs(ncRNAs)controlcellularprogramsbyaffectingprotein-codinggenes,butevidenceincreasinglypointstotheirinvolvementinanetworkofncRNA-ncRNAinteractions.Here,weshowthatalongncRNA,Uc.283+A,controlspri-miRNAprocess-ing.Regulationrequirescomplementaritybetweenthelowerstemregionofthepri-miR-195transcriptandanultraconservedsequenceinUc.283+A,whichpreventspri-miRNAcleavagebyDrosha.MutationofthesiteineitherRNAmoleculeuncouplesregulationinvivoandinvitro.Weproposeamodelinwhichlower-stemstrandinvasionbyUc.283+Aimpairsmicroprocessorrecognitionandefficientpri-miRNAcropping.InadditiontoidentifyingacaseofRNA-directedregulationofmiRNAbiogenesis,ourstudyrevealsregulatorynetworksinvolvingdifferentncRNAclassesofimportanceincancer.INTRODUCTIONGlobaltranscriptomicanalysishasrevealedagrowingnumberofhighlydiversenoncodingRNAs(ncRNAs)withactiverolesingeneregulation.Ithasbeenestimatedthatonly2%ofthegenomeistranscribedintoprotein-codingRNAs(Kapranovetal.,2007),sothelargestfractionofthetranscriptomecorrespondstonon-codingtranscripts,whichhavetraditionallybeengroupedintoclassesaccordingtotheirlengthandthensubclassifiedo...
