ArticleMethylationofStructuredRNAbythem6AWriterMETTL16IsEssentialforMouseEmbryonicDevelopmentGraphicalAbstractHighlightsdStructureoftheMETTL16m6AwriterdomainwithauniqueN-terminalmoduledN-terminalmoduleofMETTL16isessentialforcharge-basedbindingtoRNAdMETTL16preferentiallymethylatesadenosineswithinstructuredRNAsdRegulationofMat2amRNAbyMettl16isessentialformouseembryonicdevelopmentAuthorsMateuszMendel,Kuan-MingChen,DavidHomolka,PascalGos,RadhaRamanPandey,AndrewA.McCarthy,RameshS.PillaiCorrespondenceramesh.pillai@unige.chInBriefMendeletal.revealthestructuralbasisforstructuredRNArecognitionbythemammalianm6AwriterMETTL16anddemonstrateitsessentialroleinmouseearlyembryonicdevelopmentviaregulationoftheSAMsynthetaseMat2amRNA.Mendeletal.,2018,MolecularCell71,986–1000September20,2018ª2018TheAuthors.PublishedbyElsevierInc.https://doi.org/10.1016/j.molcel.2018.08.004MolecularCellArticleMethylationofStructuredRNAbythem6AWriterMETTL16IsEssentialforMouseEmbryonicDevelopmentMateuszMendel,1,3Kuan-MingChen,1,3DavidHomolka,1PascalGos,1RadhaRamanPandey,1AndrewA.McCarthy,2andRameshS.Pillai1,4,*1DepartmentofMolecularBiology,ScienceIII,UniversityofGeneva,30QuaiErnest-Ansermet,CH-1211Geneva4,Switzerland2EuropeanMolecularBiologyLaboratory,GrenobleOutstation,71AvenuedesMartyrs,38042Grenoble,France3Theseauthorscontributedequally4LeadContact*Correspondence:ramesh.pillai@unige.chhttps://doi.org/10.1016/j.molcel.2018.08.004SUMMARYInternalmodificationofRNAswithN6-methyladeno-sine(m6A)isahighlyconservedmeansofgeneexpressioncontrol.WhiletheMETTL3/METTL14het-erodimeraddsthismarkonthousandsoftranscriptsinasingle-strandedcontext,thesubstraterequire-mentsandphysiologicalrolesofthesecondm6AwriterMETTL16remainunknown.HerewedescribethecrystalstructureofhumanMETTL16torevealamethyltransferasedomainfurnishedwithanextraN-terminalmodule,whichtogetherformadeep-cutgroovethatisessentialforRNAbinding.WhenpresentedwitharandompoolofRNAs,METTL16se-lectsformethylation-structuredRNAswherethecrit-icaladenosineispresen...
