ArticleDeregulatedExpressionofMammalianlncRNAthroughLossofSPT6InducesR-LoopFormation,ReplicationStress,andCellularSenescenceGraphicalAbstractHighlightsdSPT6promotestheselectivedistributionofH3K36me3overprotein-codinggenesdSPT6lossleadstoformationofextendedlncRNAsthatarepronetoR-loopformationdDeregulatedPolIIcollideswithDNAreplisomesonlncRNAgenesdCollisionbetweenPolIIandDNAreplisomeleadstocellularsenescenceAuthorsTakayukiNojima,MichaelTellier,JonathanFoxwell,...,AshishDhir,ShonaMurphy,NickJ.ProudfootCorrespondencetaka.nojima@path.ox.ac.uk(T.N.),shona.murphy@path.ox.ac.uk(S.M.),nicholas.proudfoot@path.ox.ac.uk(N.J.P.)InBriefNojimaandcolleaguesdemonstratethatlossofhumanSPT6proteinelevateslevelsofnoncodingtranscriptionandperturbsitstermination.ThederegulatednoncodingtranscriptionincreasesR-loopformationwithconsequentDNAdamage,transcription-replicationcollision,andcellularsenescence.Thisimpliesthatnoncodingtranscriptionisrestrictedtoavoidsuchconflictsinproliferatingcells.Nojimaetal.,2018,MolecularCell72,970–984December20,2018ª2018TheAuthors.PublishedbyElsevierInc.https://doi.org/10.1016/j.molcel.2018.10.011MolecularCellArticleDeregulatedExpressionofMammalianlncRNAthroughLossofSPT6InducesR-LoopFormation,ReplicationStress,andCellularSenescenceTakayukiNojima,1,2,3,*MichaelTellier,1,2JonathanFoxwell,1ClaudiaRibeirodeAlmeida,1SueMeiTan-Wong,1SomduttaDhir,1GwendalDujardin,1AshishDhir,1ShonaMurphy,1,3,*andNickJ.Proudfoot1,3,4,*1SirWilliamDunnSchoolofPathology,UniversityofOxford,SouthParksRoad,OxfordOX13RE,UK2Theseauthorscontributedequally3Seniorauthor4LeadContact*Correspondence:taka.nojima@path.ox.ac.uk(T.N.),shona.murphy@path.ox.ac.uk(S.M.),nicholas.proudfoot@path.ox.ac.uk(N.J.P.)https://doi.org/10.1016/j.molcel.2018.10.011SUMMARYExtensivetractsofthemammaliangenomethatlackprotein-codingfunctionarestilltranscribedintolongnoncodingRNA.WhiletheselncRNAsaregenerallyshortlived,lengthrestricted,andnon-polyadeny-lated,howtheirexpressionisdistinguishedfromprotein-codinggenesremai...
