ReviewEmergingRolesofUbiquitin-likeProteinsinPre-mRNASplicingSittinanChanarat1,2,*andShravanKumarMishra3,*Ubiquitin-likeproteins(UBLs)belongtotheproteinfamilywhosemembersshareaglobularbeta-graspfoldstructure.Thearchetypalmember,ubiquitin,isknownforitsfunctioninproteasome-mediatedproteindegradation.UBLshavebeenshowntoplayseveralcrucialrolesbesidesproteinturnover,includingDNAdamageresponse,cellcyclecontrol,cellularsignaling,proteintrafficking,andinnateimmunityactivation.Inthepastfewyears,accumulatingevidenceillustratesthatfourUBLs,namely,ubiquitin,SUMO,Hub1,andSde2,areinvolvedineukaryoticpre-mRNAsplicing.Theymodifythespliceosomesandpromotesplicingbyaddingnewsurfacesforintermolecularinteractions,therebyrefiningtheoutcomeofgeneexpression.Inthisreviewarticle,wehighlightrecentdiscoverieswithanemphasisontheemergingrolesofUBLsinsplicingregulation.Ubiquitin-likeProteinFamilyAddsAnotherLayerofSplicingControlPre-messengerRNAsplicingisoneofthefundamentalprocessesineukaryoticcellsthatremovesnoncodingintronicsequencesfrompre-mRNAsandligatesprotein-codingexons.Thereactioniscatalyzedbyamulti-megadaltonribonucleoproteincomplex,thespliceosome(seeGlossary)comprisingfivesmallnuclearRNAsandmorethan300proteins[1–4].Thesecomponentsassembleonpre-mRNAsinastepwisemannertoformactivespliceosomeswhoseconformationandcompositionarehighlydynamicyettightlyregulated[4,5].Spliceo-somalregulationbecomesessentialsinceanymissplicingdirectlyaffectsgeneexpressionthatcould,inturn,resultincellulardysfunction,celldeath,anddiseases[6].Tocircumventpotentialdeleteriouseffectsofaberrantsplicing,pre-mRNAsplicingiscontrolledbyabroadrangeofmolecularactivitiesthatincludesprotein–protein,protein–RNA,orRNA–RNAinteractions,andpost-translationalmodificationsofspliceosomalcomponents[4,5,7–11].UBLsfunctionascentralregulatorsofalargenumberofprocessesineukaryoticcells[12–14].ThearchetypalmemberoftheUBLfamily,ubiquitin,modifiesproteinsbycovalentlyconjugatingtothee-aminogroupoftargetlysines[13,15].Dependingontheubiqu...
