ReviewSplicingtoKeepCycling:TheImportanceofPre-mRNASplicingduringtheCellCycleMayraPetasny,1MercedesBentata,1AndreaPawellek,2MaiBaker,1GillianKay,1andMaayanSalton,1,*,@Pre-mRNAsplicingisafundamentalprocessinmammaliangeneexpression,andalternativesplicingplaysanextensiveroleingeneratingproteindiversity.Becausethemajorityofgenesundergopre-mRNAsplicing,mostcellularpro-cessesdependonproperspliceosomefunction.Wefocusonthecellcycleanddescribeitsdependenceonpre-mRNAsplicingandaccuratealternativesplicing.Weoutlinethekeycell-cyclefactorsandtheirknownalternativesplicingisoforms.Wediscussdifferentlevelsofpre-mRNAsplicingregulationsuchaspost-translationalmodificationsandchangesintheexpressionofsplicingfactors.Wedescribetheeffectofchromatindynamicsonpre-mRNAsplicingduringthecellcycle.Inaddition,wefocusonspliceosomecomponentSF3B1,whichismutatedinmanytypesofcancer,anddescribethelinkbetweenSF3B1anditsinhibitorsandthecellcycle.Pre-mRNAsplicingoccursin97%ofhumangenes.Thissuggeststhatmostifnotallcellularprocessesaredependentonthesplicingmachinery.Wefocushereonthecellcycleanddiscussitsmanyconnectionstopre-mRNAsplicing.Splicingisregulatedbybothsplicingfactorsandchromatin,whichareknowntoalterduringthecellcycle.Wereviewthechangesinthesetworegulatorsandtheireffectonthecellcycle.CellCycleThecell-cycleprocessishighlyconservedandpreciselycontrolledforgenomereplication.Itconsistsoffourdistinctphases,G0/G1,S(DNAsynthesis),G2,andM(mitosis),whichhavemul-tiplecheckpoints.ThesecheckpointsensurereliableDNAreplicationinSphaseandtheexactdi-visionofthechromosomesintodaughtercells.Ensuringthatallchromosomesarealignedcorrectlyonthemitoticspindlebeforedivisionofthetwodaughtercellspreventsdead,aneuploid,ormutantcells.TheG1andG2phasesserveasgapsbetweentheSandMphases.G1isthepointwherethedecisionismadewhethertoenterSphaseandreplicatetheDNAorexitthecellcycleandenterG0.G2ensuresfullreplicationofthegenomeinSphaseandthetransitiontocelldivisioninMphase.Cell-cycledecisionsaremadebyassessingbothintra-andextracellul...
