Small Regulatory RNAs May Sharpen Spatial Expression Patterns 英文参考文献.docVIP

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Small Regulatory RNAs May Sharpen Spatial Expression Patterns 英文参考文献.doc

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Small Regulatory RNAs May Sharpen Spatial Expression Patterns 英文参考文献

SmallRegulatoryRNAsMaySharpenSpatial ExpressionPatterns Erel Levine[,Peter McHale[,Herbert Levine* CenterforTheoreticalBiologicalPhysics,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Thepreciseestablishmentofgeneexpressionpatternsisacrucialstepindevelopment.Formationofasharpboundary betweenhighandlowspatialexpressiondomainsrequiresageneticmechanismthatexhibitssensitivity,yetisrobust tofluctuations,ademandthatmaynotbeeasilyachievedbymorphogensalone.Recently,ithasbeendemonstrated thatsmallRNAs(and,inparticular,microRNAs)playmanyrolesinembryonicdevelopment.WhereassomeRNAsare essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here, we explorethepossibilitythatsmallRNAsparticipateinsharpeningageneexpressionprofilethatwascrudelyestablished byamorphogen.Tothisend,westudyamodelinwhichsmallRNAsinteractwithatargetgeneanddiffusivelymove fromcelltocell.Thoughdiffusiongenerallysmoothensspatialexpressionpatterns,wefindthatintercellularmobility ofsmallRNAsisactuallycriticalinsharpeningtheinterfacebetweentargetexpressiondomainsinarobustmanner. This sharpening occurs as small RNAs diffuse into regions of low mRNA expression and eliminate target molecules therein,butcannotaffectregionsofhighmRNAlevels.Wediscusstheapplicabilityofourresults,asexamples,tothe caseofleafpolarityestablishmentinmaizeandHoxpatterningintheearlyDrosophilaembryo.Ourfindingspointout the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of theirinteractions.ThesepropertiesareyettobeestablisheddirectlyformostclassesofsmallRNAs.Anindirectyet simpleexperimentaltestoftheproposedmechanismissuggestedinsomedetail. Citation: Levine E, McHale P, Levine H (2007) Small regulatory RNAs may sharpen spatial expression patterns. PLoS Comput Biol 3(11): e233. doi: 10.1371/journal.pcbi. 0030233 ultrasensitivity [6]. As an example, in Drosophila early embryonic development, Hunchback tran