A SteMNess perspective of survival motor neuron function： splicing factors in stem cell biology and disease.pdfVIP

Front．Bio1．2015，l0(4)：297309 D0I10．1007／s11515．015—1368．9 ASteMNessperspectiveofsurvivalmotorneuronfun 10n： splicingfactorsIinstem celIlbiologyandddhsease smratJ．Grice，Ji-LongLiu(函) MRCFunctionalGenomicsUnit,DepartmentofPhysiology,AnatomyandGenetics．UniversityofOxford,SouthParksRoad, OxfordOX13PT,UK ◎HigherEducationPressandSpringer-VerlagBerlinHeidelberg2015 Abstract Genome—wide ana13rsesofmetazoan messengerRNA (mRNA)speciesareunveiling the extensive transcriptionaldiversitygeneratedbyalternativesplicing (AS)．Researchisalsobeginningtoidentifythesplicing faetorsandASeventsrequiredtomaintainthebalancebetweenstem cellrenewalfi．esternnessproperties)and difflerentiation．0uesetofproteinsatthecenterofspliceosomebiogenesisarethesurvivalmotorneuronfSM N1complex constituents，whichhaveacriticalroleintheassemblyofspliceosomalsmallnuclearrib0nucle0proteins(snRNPs)inall celis．Inthisreview wediscusswhatiscurrentlyknownabouthow AScontrolspluripotencyandcellfateandconsider howanincreasedrequirem entforsplicingfactors，includingSMN 。helpstomaintainanenrichmentofstem cell—specific ASevents．Furthermore．wehighlightstudiesshowingthatmutationsinspecificsplicingfactorscanleadtotheaberrant development，andcausetargeteddegeneration ofthenervoussystem．Using SM N asanexample。wediscussthe perspectiveofhow stem cell-specificchangesin splicingfactorscan leadtodevelopm entaldefectsandtheselective degenerationofparticulartissues．FinallyweconsidertheexpandingroleofSMN．andothersplicingfactors。inthe regulationofgeneexpressionin stem cellbiology,therebyprovidinginsightintoanumberofdebilitatingdiseases． Keywords stemcells，splicing，survivalmotorneuron(SMN)，spinalmuscularatrophy(SMA) Introduction Loheta1．，2006；Cheneta1．，2008；Dixoneta1．，20151．In additiontothis，advancesraenow showinghow ASgenerates Theadvent0ftechnologiesthatenablethedeepsequencingof stem eellspecificmRNA isofo