ArticleRegulatoryExpansioninMammalsofMultivalenthnRNPAssembliesthatGloballyControlAlternativeSplicingGraphicalAbstractHighlightsdMammalian-specificalternativeexonsimpacttyrosine-richdisorderedregionsdLong-rangeRNAduplexescontrolsplicingoftheseexonsinhnRNPsdTheexonspromotemultivalentassembliesonpre-mRNAtogloballycontrolsplicingdEvolutionofexonskippinginhnRNPsexpandedtheregulatorycapacityofmammalsAuthorsSergeGueroussov,RobertJ.Weatheritt,DaveO’Hanlon,Zhen-YuanLin,AshrutNarula,Anne-ClaudeGingras,BenjaminJ.BlencoweCorrespondenceserge.gueroussov@utoronto.ca(S.G.),b.blencowe@utoronto.ca(B.J.B.)InBriefMammalian-specificalternativeexonscontroltheformationoftyrosine-dependentmulti-hnRNPassembliesthat,inturn,globallyregulatesplicingpatterns.Gueroussovetal.,2017,Cell170,324–339July13,2017ª2017ElsevierInc.http://dx.doi.org/10.1016/j.cell.2017.06.037ArticleRegulatoryExpansioninMammalsofMultivalenthnRNPAssembliesthatGloballyControlAlternativeSplicingSergeGueroussov,1,2,5,*RobertJ.Weatheritt,1,3,5DaveO’Hanlon,1Zhen-YuanLin,4AshrutNarula,1,2Anne-ClaudeGingras,2,4andBenjaminJ.Blencowe1,2,6,*1DonnellyCentre,UniversityofToronto,Toronto,ON,Canada2DepartmentofMolecularGenetics,UniversityofToronto,Toronto,ON,Canada3MRCLaboratoryofMolecularBiology,FrancisCrickAvenue,Cambridge,UK4Lunenfeld-TanenbaumResearchInstitute,MountSinaiHospital,Toronto,ON,Canada5Theseauthorscontributedequally6LeadContact*Correspondence:serge.gueroussov@utoronto.ca(S.G.),b.blencowe@utoronto.ca(B.J.B.)http://dx.doi.org/10.1016/j.cell.2017.06.037SUMMARYAlternativesplicing(AS)patternshavedivergedrapidlyduringvertebrateevolution,yetthefunctionsofmostspecies-andlineage-specificsplicingeventsarenotknown.Weobservethatmammalian-specificASeventsareenrichedintranscriptsequencesen-codingintrinsicallydisorderedregions(IDRs)ofpro-teins,inparticularthosecontainingglycine/tyrosinerepeatsthatmediateformationofhigher-orderpro-teinassembliesimplicatedingeneregulationandhu-mandisease.Theseevolutionarychangesimpactnearlyallmember...
