ArticlePNPT1ReleasefromMitochondriaduringApoptosisTriggersDecayofPoly(A)RNAsGraphicalAbstractHighlightsdGlobaldecayofpolyadenylatedRNAsdependsonMOMPandbeginsatthe30endd30to50exoribonucleasePNPT1isreleasedfrommitochondriaduringMOMPdPNPT1initiatesapoptoticRNAdecayandpromotesapoptosisd30structuresorproteinbindingofnoncodingRNAspreventtheirdegradationbyPNPT1AuthorsXingLiu,RuiFu,YoudongPan,KarlaF.Meza-Sosa,ZhibinZhang,JudyLiebermanCorrespondencejudy.lieberman@childrens.harvard.eduInBriefWidespreadRNAdecayduringapoptosisisinitiatedbythemitochondrialexoribonucleasePNPT1.DataResourcesGSE104602Liuetal.,2018,Cell174,187–201June28,2018ª2018ElsevierInc.https://doi.org/10.1016/j.cell.2018.04.017ArticlePNPT1ReleasefromMitochondriaduringApoptosisTriggersDecayofPoly(A)RNAsXingLiu,1,2,4RuiFu,1,2,4YoudongPan,3KarlaF.Meza-Sosa,1,2ZhibinZhang,1,2andJudyLieberman1,2,5,*1PrograminCellularandMolecularMedicine,BostonChildren’sHospital,Boston,MA02115,USA2DepartmentofPediatrics,HarvardMedicalSchool,Boston,MA02115,USA3DepartmentofDermatologyandHarvardSkinDiseaseResearchCenter,BrighamandWomen’sHospital,Boston,MA02115,USA4Theseauthorscontributedequally5LeadContact*Correspondence:judy.lieberman@childrens.harvard.eduhttps://doi.org/10.1016/j.cell.2018.04.017SUMMARYWidespreadmRNAdecay,anunappreciatedfeatureofapoptosis,enhancescelldeathanddependsonmitochondrialoutermembranepermeabilization(MOMP),TUTases,andDIS3L2.WhichRNAsaredecayedandthedecay-initiatingeventareunknown.Here,weshowextensivedecayofmRNAsandpoly(A)noncoding(nc)RNAsatthe30end,triggeredbythemitochondrialintermembranespace30-to-50exoribonucleasePNPT1,releasedduringMOMP.PNPT1knockdowninhibitsapoptoticRNAdecayandreducesapoptosis,whileectopicexpressionofPNPT1,butnotanRNase-deficientmutant,increasesRNAdecayandcelldeath.The30endofPNPT1substratesthreadthroughanarrowchannel.Manynon-poly(A)ncRNAscontain30-secondarystructuresorbindproteinsthatmayblockPNPT1activity.Indeed,mutationsthatdisruptthe30-stem-loopofadecay-resistantncRNArenderthetra...
