Publishedonline25July2020NucleicAcidsResearch,2020,Vol.48,No.158509–8528doi:10.1093/nar/gkaa594TheRNAexosomeshapestheexpressionofkeyprotein-codinggenesMengjunWu1,EvdoxiaKaradoulama1,2,MartaLloret-Llinares2,3,JeromeOlivierRouviere2,ChristianSkovVaagensø1,MartinMoravec2,BingnanLi4,JingwenWang4,GuifenWu2,MariaGockert2,VicentPelechano4,TorbenHeickJensen2,*andAlbinSandelin1,*1TheBioinformaticsCentre,DepartmentofBiologyandBiotechandResearchInnovationCentre,UniversityofCopenhagen,OleMaaløesVej5,DK2200CopenhagenN,Denmark,2DepartmentofMolecularBiologyandGenetics,AarhusUniversity,C.F.MøllersAlle3,Building1130,Aarhus8000,Denmark,3EuropeanBioinformaticsInstitute(EMBL-EBI),EuropeanMolecularBiologyLaboratory,WellcomeGenomeCampus,Hinxton,CambridgeCB101SD,UKand4SciLifeLab,DepartmentofMicrobiology,TumorandCellBiology,KarolinskaInstitutet,Solna17165,SwedenReceivedApril13,2020;RevisedJune29,2020;EditorialDecisionJuly01,2020;AcceptedJuly03,2020ABSTRACTTheribonucleolyticexosomecomplexiscentralfornuclearRNAdegradation,primarilytargetingnon-codingRNAs.Still,thenuclearexosomecouldhaveprotein-coding(pc)gene-specificregulatoryactiv-ities.Bydepletinganexosomecorecomponent,orcomponentsofexosomeadaptorcomplexes,weidentify∼2900transcriptionstartsites(TSSs)fromwithinpcgenesthatproduceexosome-sensitivetranscripts.Atleast1000oftheseoverlapwithan-notatedmRNATSSsandaconsiderableportionoftheirtranscriptssharetheannotatedmRNA3′end.Weidentifytwotypesofpc-genes,bothemploy-ingasingle,annotatedTSSacrosscells,butthefirsttypeprimarilyproducesfull-length,exosome-sensitivetranscripts,whereasthesecondprimarilyproducesprematurelyterminatedtranscripts.Geneswithintheformertypeoftenbelongtoimmediateearlyresponsetranscriptionfactors,whilegeneswithinthelatterarelikelytranscribedasacon-sequenceoftheirproximitytoupstreamTSSsontheoppositestrand.Conversely,whengeneshavemultipleactiveTSSs,alternativeTSSsthatproduceexosome-sensitivetranscriptstypicallydonotcon-tributesubstantiallytooverallgeneexpression,andmostsuc...
