REVIEWOpenAccessm6A-bindingproteins:theemergingcrucialperformersinepigeneticsYanchunZhao,YuanfeiShi,HuafeiShenandWanzhuoXie*AbstractN6-methyladenosine(m6A)isawell-knownpost-transcriptionalmodificationthatisthemostcommontypeofmethylationineukaryoticmRNAs.Theregulationofm6Aisdynamicandreversible,whichiserectedbym6Amethyltransferases(“writers”)andremovedbym6Ademethylases(“erasers”).Notably,theeffectsontargetedmRNAsresultedbym6Apredominantlydependonthefunctionsofdifferentm6A-bindingproteins(“readers”)includingYT521-Bhomology(YTH)domainfamily,heterogeneousnuclearribonucleoproteins(HNRNPs),andinsulin-likegrowthfactor2mRNA-bindingproteins(IGF2BPs).Indeed,m6AreadersnotonlyparticipateinmultipleproceduresofRNAmetabolism,butalsoareinvolvedinavarietyofbiologicalprocesses.Inthisreview,wesummarizedthespecificfunctionsandunderlyingmechanismsofm6A-bindingproteinsintumorigenesis,hematopoiesis,virusreplication,immuneresponse,andadipogenesis.Keywords:N6-methyladenosine,m6A-bindingproteins,Cancer,Virus,Immunity,AdipogenesisIntroductionEpigeneticabnormalities,suchasDNAmethylation,his-tonemodification,genomicimprinting,andchromo-someremodeling,mainlyaffectthecharacteristicsandfunctionsofgenesthroughregulatingthetranscriptionortranslationprocesses[1],withoutalteringtheDNAsequences.Thesechangesingeneexpressionarestableduringcellself-renewal,division,anddifferentiation.Overthepastdecades,moreandmoreattentionhasbeenpaidtoRNAmodificationwiththehelpofhigh-throughputsequencing.Todate,morethan100typesofmodificationshavebeenconfirmedinvariousRNAs,in-cludingmessengerRNAs(mRNAs),transferRNAs(tRNAs),ribosomalRNAs(rRNAs),microRNAs(miR-NAs),andlongnon-codingRNAs(lncRNAs).Notably,N6-methyladenosine(m6A),awell-knownpost-transcriptionalmodificationfirstdiscoveredandpro-posedin1974,hasbeenregardedasthemostprevalentmethylationineukaryoticmRNAs[2,3].Itisestimatedthatabout0.1–0.4%ofalladeninesarespeciallymodi-fiedbym6AinmRNAs[4].m6AusuallyappearsattheRRACHsequences(R=A,G,orU;R=AorG;andH=A,C,orU)[5,...
