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1、Homer1AlternativeSplicingIsRegulatedbyGonadotropin-ReleasingHormoneandModulatesGonadotropinGeneExpressionQianWang,MariaD.Chikina,HannaPincas,StuartC.SealfonCenterforTranslationalSystemsBiology,DepartmentofNeurology,andFriedmanBrainInstitute,IcahnSchoolofMedicineatMou
2、ntSinai,NewYork,NewYork,USAHypothalamicgonadotropin-releasinghormone(GnRH)playsacriticalroleinreproductivephysiologybyregulatingfollicle-stimulatinghormone(FSH)andluteinizinghormone(LH)geneexpressioninthepituitary.Analysisofgonadotropedeep-se-quencingdataidentifiedagl
3、obalregulationofpre-mRNAsplicingbyGnRH.Homer1,ageneencodingapostsynapticdensityscaffoldingprotein,wasselectedforfurtherstudy.Homer1expressesashortspliceform,Homer1a,andmore-abundantlongtranscriptsHomer1b/c.GnRHinducedamodestincreaseinHomer1b/cexpressionandadramaticin
4、creaseintheHomer1aspliceform.GproteinknockdownstudiessuggestedthattheHomer1induction,butnottheregulatedsplicing,wasGq/11de-Downloadedfrompendent.PhosphorylationofthesplicingregulatorSRp20wasfoundtobeinducedbyGnRH.SRp20depletionattenuatedtheGnRH-inducedincreaseintheH
5、omer1a-to-Homer1b/cratioandmodulatedtheeffectsofGnRHonFSHandLHexpression.Homer1geneknockdownresultedinincreasedGnRH-inducedFSHandLHtranscriptlevels.Furthermore,splice-form-spe-cificreductionofHomer1b/cincreasedbothFSHandLHmRNAinduction,whereasreductionofHomer1ah
6、adtheoppositeeffectonFSHinduction.TheseresultsindicatethattheregulationofHomer1splicingbyGnRHcontributestogonadotropingenecontrol.http://mcb.asm.org/Gonadotropin-releasinghormone(GnRH)playsacentralroleprocesscanleadtotheexpressionoffunctionallydistinctproteinsinthec
7、ontrolofnormalreproductivefunctionbyregulatingfromthesamegeneinatemporalortissue-specificfashion.Aboutthesynthesisandreleaseofthegonadotropinsluteinizinghor-95%ofhumangenesundergoalternativesplicing(18).Mechanis-mone(LH)andfollicle-stimulatinghormone(FSH)bypituitaryti
8、cally,splicingregulatorsarekeymodulatorsofsplicesitechoicegonadotropes.Thesetwohormonesareheterodimericproteinsviainteractionwithth
