FeatureReviewLongNoncodingRNAsinHost–PathogenInteractionsFedericaAgliano,1VijayA.Rathinam,1AndreiE.Medvedev,1SivapriyaKailasanVanaja,1,*andAnthonyT.Vella1,*LongnoncodingRNAs(lncRNAs)arekeymoleculesthatregulategeneexpres-sioninavarietyoforganisms.LncRNAscandrivedifferenttranscriptionalandpost-transcriptionaleventsthatimpactcellularfunctions.RecentstudieshaveidentifiedmanylncRNAsassociatedwithimmunecelldevelopmentandacti-vation;however,anunderstandingoftheirfunctionalroleinhostimmunitytoinfectionisjustemerging.Here,weprovideadetailedandupdatedreviewofthefunctionalrolesoflncRNAsinregulatingmammalianimmuneresponsesduringhost–pathogeninteractions,becausethesefunctionsmaybeeitherbeneficialordetrimentaltothehost.WithincreasedmechanisticinsightintotherolesoflncRNAs,itmaybepossibletodesignand/orimprovelncRNA-basedtherapiestotreatavarietyofinfectiousandinflammatorydiseases.LncRNAs:Identification,Characteristics,andClassificationItiswellknownthat<2%ofthemammaliangenomeencodesproteins,whiletheremaininggenesencodenonprotein-codingRNAs[1].ncRNAscanbedividedintosmallncRNAsandlncRNAs.LncRNAsarenoncodingRNAstranscribedbyRNApolymeraseII(RNAPolII)andarelongerthan200nucleotides.Thisarbitrarycut-offinsizedistinguishesthemfromsmallncRNAs,suchasmiRNAsandshortinterferingRNAs(siRNAs).SimilartomiRNAs,lncRNAshaveemergedasnewregulatorsoftheexpressionofinflammatoryresponsegenesinmammalianleukocytes[2].Inaddition,similartomRNAs,mostlncRNAsarecapped,polyadenylated,andspliced[3].Further-more,acomprehensiveanalysisoftheirexpressioninmultiplehumanorganshasindicatedthatlncRNAsmaybemoretissuespecificthanareprotein-codinggenes,albeitwithlowerexpressionthanthelatter[4].WhilesomelncRNAshavebeenreportedtoencodesmallpeptides[5,6],thefunctionalsignificanceofsuchpeptidesisoftenunclear;and,forthepurposeofthisreview,arenotdiscussedhere;however,readersaredirectedtootherexcellentreviews[7,8].LncRNAsareclassifieddependingontheirgenomiclocation(Box1).Sofar,fourclassesoflncRNAareknown:longintergenicncRNAs(linc...
