NuclearProximityofMtr4withRNAexosomerestrictsDNAmutationalasymmetryJunghyunLim1,#,PankajKumarGiri1,#,*,DavidKazadi1,BriceLaffleur1,WanweiZhang1,VeronikaGrinstein1,EvangelosPefanis1,LewisM.Brown2,ErikLadewig3,OphélieMartin4,YulingChen5,RaulRabadan3,FrançoisBoyer4,GersonRothschild1,MichelCogné4,EricPinaud4,HaitengDeng5,andUttiyaBasu1,*,§1DepartmentofMicrobiologyandImmunology,CollegeofPhysiciansandSurgeons,ColumbiaUniversity,NewYork,NY100322QuantitativeProteomicsCenter,DepartmentofBiologicalSciences,ColumbiaUniversity,NewYork,NY100273DepartmentsofSystemsBiologyandBiomedicalInformatics,CollegeofPhysiciansandSurgeons,ColumbiaUniversity,NewYork,NY100324UniversitédeLimoges,CentreNationaldelaRechercheScientifique,CHULimoges,CRIBL,UMR7276,FA87000Limoges,France5SchoolofLifeSciences,TsinghuaUniversity,Beijing,ChinaSUMMARYThedistributionofsenseandantisensestrandDNAmutationsontranscribedduplexDNAcontributestothedevelopmentofimmuneandneuralsystemsalongwiththeprogressionofcancer.BecausedevelopmentallymaturedBcellsundergobiologicallyprogrammedstrand-specificDNAmutagenesisatfocalDNA/RNAhybridstructures,theymakeaconvenientsystemtoinvestigatestrand-specificmutagenesismechanisms.WedemonstratethatthesenseandantisensestrandDNAmutagenesisattheimmunoglobulinheavychainlocusandsomeotherregionsoftheBcellgenomedependsuponlocalizedRNAprocessingproteincomplexformationinthenucleus.BoththephysicalproximityandcoupledactivitiesofRNAhelicaseMtr4(andSenataxin)withthenoncodingRNAprocessingfunctionofRNAexosomedeterminethestrandspecificdistributionof*Correspondence:pg2501@cumc.columbia.edu;ub2121@cumc.columbia.edu.#co-firstauthor§LeadContactPublisher'sDisclaimer:ThisisaPDFfileofanuneditedmanuscriptthathasbeenacceptedforpublication.Asaservicetoourcustomersweareprovidingthisearlyversionofthemanuscript.Themanuscriptwillundergocopyediting,typesetting,andreviewoftheresultingproofbeforeitispublishedinitsfinalcitableform.Pleasenotethatduringtheproductionprocesserrorsmaybediscoveredwhichcouldaffecttheco...
