©2014LandesBioscience.DonotdistributePoint-of-Viewwww.landesbioscience.comRnABiology669RnABiology11:6,669–672;June2014;©2014LandesBiosciencePoint-of-ViewPoint-of-ViewPoint-of-ViewN6-methyladenosine(m6A)isaprevalentmodificationofeukaryoticmRNAs.Itregulatesyeastcellfateandisessentialtothedevelopmentandfertilityofmetazoans.AlthoughitspresenceinmRNAhasbeenknownsincetheearly1970s,thefunctionofm6Aremainedamysteryuntilthespateofdiscoveriesinthepastthreeyears.Here,wefocusonthediscoveryofm6A“readers”(proteinsthatspecificallyrecognizem6A),andtheirfunctionsintuningmRNAstability,aswellasthebroadersignificanceofsuchm6A-dependentregulationofgeneexpression.EukaryoticmRNAs(mRNAs)notonlyencodepreciseproteinsequence,butalsoconveyinformationfortheirprocessing,transportation,translation,anddecay,therebycollectivelycreatingacomplexlayerofgeneregulationatthepost-transcriptionalstage.KnownmechanismsinvolvingRNAstructure,microRNA,andtranslationregulationallcontributetopost-transcriptionalregulationofgeneexpression.EstablishedregulatorymodesofmRNAinvolveshortRNAsequencesinuntranslatedregions(UTRs)asexemplifiedbyAU-richelement(stability),iron-responsiveelement(translation),zipcodeelement(localization),microRNAseedingsequences(translationandstability),andthemRNAcapandpolyadenylatedtail.Inthispaper,wediscussanewmechanismofregulation:reversibleinternalRNAmethylation.EssentialDescriptionofm6AN6-methyladenosine(m6A)isamajorinternal(non-cap)modificationofeukaryoticmRNA(mRNA).1Onaverage,everymRNAhasthreem6AresidueswithinacontextofG(m6A)C(70%)orA(m6A)C(30%).2Recentadvancesinm6A-sequencingtechnologyhavealsorevealedm6Aenrichmentinlongexonsandaroundthestopcodon.3-5Despitethewidespreaddistributionofm6Asitesover7000humantranscripts,them6AcontentofindividualmRNAsisnon-uniform;eachm6Asitecanbenon-stoichiometricwhilesomemRNAsarefreeofm6A.1m6Aispost-transcriptionallyinstalledbyanm6Amethyltransferasecomplex1,6incoordinationwithothermRNAprocessingevents,namely3'polyadenylation,5'capping,andsplicing.Ina...
