Upf1 contributes to Arc/Arg3.1gene expression
- Title
- Upf1 contributes to Arc/Arg3.1gene expression
- Authors
- 류혜국; JI, YOUNG SEO; Eunju Lee; 김은아; YOUNGSEOB, JUNG; KIM, HYOJIN; EUNJI, OH; Do-Yeon Kim; KIM, KYONG TAI
- Date Issued
- 2017-11-14
- Publisher
- SFN
- Abstract
- spatiotemporallocalizationinordertocarryouttheircriticalfunctions.ThemRNAtranscriptforthesynapticprotein,Activity-regulatedcytoskeleton-associatedprotein(Arc,alsoknownasArg3.1),containstwoconserved3’untranslatedregion(UTR)introns,andconsequently,wasproposedanaturaltargetfornonsense-mediatedmRNAdecay(NMD).
ThismechanismwasthoughttofunctionasacriticalbrakeonArcproteinsynthesis,allowingprecisecontrolofgeneexpression.TheRNAhelicaseUpf1isamajorcomponentoftheNMDmachinery,however,aspecificroleforthisproteinintheregulationofArcgeneexpressionremainsunclear.Here,wedemonstratethatUpf1functionsatthetranscriptionalandtranslationalleveltopromotealowbasallevelofArcgeneexpression.Specifically,
Upf1suppressesArctranscriptionbyenhancingdestabilizationofmRNAsencodingvarioustranscriptionfactors.Upf1alsobindstotheArc3’UTR,resultingintranslationalsuppression.Surprisingly,however,theArctranscriptescapesfromUpf1-mediatedNMDbybindingtoAgo2/miRISC,whichblocksNMDandfurthersuppressesArcmRNAtranslation.Finally,weshowthatsustainedArcexpressionresultingfromreducedlevelsofUpf1contributestoCofilinhyperphosphorylationandabnormalneuronaloutgrowth.
Collectively,thesedatarevealanewparadigmforArcgeneregulationandsuggestthatmultiplelevelsofUpf1-mediatedinhibitionmayallowneuronstomorerapidlyandeffectivelyrespondtochangesinneuronalactivity.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/42740
- Article Type
- Conference
- Citation
- Society of Neuroscience Annual Meeting 2017, 2017-11-14
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