Regulationoflongnon-codingRNAsandgenomedynamicsbytheRNAsurveillancemachineryLekhaNair,HachungChung,UttiyaBasuDepartmentofMicrobiologyandImmunology,VagelosCollegeofPhysiciansandSurgeons,ColumbiaUniversity,NewYorkCity,NY,USA.AbstractMuchofthemammaliangenomeistranscribed,generatinglongnon-codingRNAs(lncRNAs)thatcanundergopost-transcriptionalsurveillancewherebyonlyasubsetofthenon-codingtranscriptsisallowedtoattainsufficientstabilitytopersistinthecellularmilieuandcontrolvariouscellularfunctions.Parallelingproteinturnoverbytheproteasomecomplex,lncRNAsarealsolikelytoexistinadynamicequilibriumthatismaintainedthroughconstantmonitoringbytheRNAsurveillancemachinery.InthisReview,wedescribetheRNAsurveillancefactorsanddiscussthevitalroleoflncRNAsurveillanceinorchestratingvariousbiologicalprocesses,includingtheprotectionofgenomeintegrity,maintenanceofpluripotencyofembryonicstemcells,antibody–genediversification,coordinationofimmunecellactivationandregulationofheterochromatinformation.WealsodiscussexamplesofhumandiseasesanddevelopmentaldefectsassociatedwiththefailureofRNAsurveillancemechanisms,furtherhighlightingtheimportanceoflncRNAsurveillanceinmaintainingcellandorganismfunctionsandhealth.Non-codingRNAs(ncRNAs)areatypeofRNAthatarenottranslatedintoproteinandincludesmallncRNAs(suchasmicroRNAs)intherangeof15–30nucleotides1–3andlongncRNAs(lncRNAs),whicharegenerallyconsideredaslongerthan200nucleotides4.LncRNAsincludeavarietyoftranscripts,allofwhichcanmodulategeneexpressioninspecificwaysbasedoncelltype,developmentalstageandfunction5–7(Box1).AsonlyafractionoflncRNAsmaybebiologicallyrelevanttoagivenprocess,cellsuseRNAsurveillancepathwaystoidentifyanddegrademostlncRNAs.RNAsurveillanceisnecessaryforgenomestabilityandgeneexpression8–10.WhereasmechanismsofmRNAsurveillancehavebeenextensivelyreviewed11,12,lessisknownaboutthesurveillanceofthediversetypesoflncRNA.AlthoughthevariouscomponentsoftheRNAsurveillancepathwaysarestillbeingcharacterized,itisknownthatendoribonucleases,5′-exoribon...
