Alu Exonization Events Reveal Features Required for Precise Recognition of Exons by the Splicing Machinery 英文参考文献.docVIP
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Alu Exonization Events Reveal Features Required for Precise Recognition of Exons by the Splicing Machinery 英文参考文献
AluExonizationEventsRevealFeaturesRequiredfor
PreciseRecognitionofExonsbytheSplicingMachinery
SchragaSchwartz,NuritGal-Mark,NirKfir,RamOren,EddoKim,GilAst*
DepartmentofHumanMolecularGeneticsandBiochemistry,SacklerFacultyofMedicine,Tel-AvivUniversity,TelAviv,Israel
Abstract
Despitedecadesofresearch,thequestionofhowthemRNAsplicingmachinerypreciselyidentifiesshortexonicislandswithin
the vast intronic oceans remains to a large extent obscure. In this study, we analyzed Alu exonization events, aiming to
understandtherequirementsforcorrectselectionofexons.ComparisonofexonizingAlustotheirnon-exonizingcounterparts
isinformativebecauseAlusinthesetwogroupshaveretainedhighsequencesimilaritybutareperceiveddifferentlybythe
splicing machinery. We identified and characterized numerous features used by the splicing machinery to discriminate
betweenAluexonsandtheirnon-exonizingcounterparts.Ofthese,themostnovelissecondarystructure:Aluexonsingeneral
andtheir59splicesites(59ss)inparticulararecharacterizedbydecreasedstabilityoflocalsecondarystructureswithrespectto
their non-exonizing counterparts. We detected numerous further differences between Alu exons and their non-exonizing
counterparts,amongothersintermsofexon–intronarchitectureandstrengthofsplicingsignals,enhancers,andsilencers.
Support vector machine analysis revealed that these features allow a high level of discrimination (AUC=0.91) between
exonizingandnon-exonizingAlus.Moreover,thecomputationallyderivedprobabilitiesofexonizationsignificantlycorrelated
withthebiologicalinclusionleveloftheAluexons,andthemodelcouldalsobeextendedtogeneraldatasetsofconstitutive
andalternativeexons.Thisindicatesthatthefeaturesdetectedandexploredinthisstudyprovidethebasisnotonlyforprecise
exonselectionbutalsoforthefine-tunedregulationthereof,manifestedincasesofalternativesplicing.
Citation:SchwartzS,Gal-MarkN,KfirN,OrenR,KimE,etal.(2009)AluExonizationEventsRevealFeaturesRequiredforPreciseRecognitionofExonsbythe
SplicingMachinery.PLoSComputBiol5(3):e
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