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HnRNPQ suppresses polyglutamineaggregation by post-transcriptional regulation of vaccinia-related kinase 2
- Title
- HnRNPQ suppresses polyglutamineaggregation by post-transcriptional regulation of vaccinia-related kinase 2
- Authors
- HYE, GUK RYU; SANGJUNE, KIM; SAEBOM, LEE; EUNJU, LEE; JI, YOUNG SEO; HYOJIN, KIM; YOUNGSEOB, JUNG; Do Yeon, Kim; KIM, KYONG TAI
- Date Issued
- 2017-05-18
- Publisher
- KSBMB
- Abstract
- Themisfoldingofproteinswithabnormallypolyglutamine(polyQ)expansioncauseneurodegenerativedisordersincludingHuntington'sdisease(HD).TCP-1ringcomplex(TRiC)/Chaperonin-containing TCP-1(CCT)hasanessentialroleinprotectingagainsttheaggregationandcytotoxicityofpolyQproteins.Notably,wehavepreviouslyshownthatvaccinia-relatedkinase2(VRK2)downregulateschaperoninTRiCproteinlevelsthroughtheubiquitin-proteasomesystembydestabilizingubiquitin-specificprotease25(USP25). VRK2expressionisknowntobemuchhigherinactivelyproliferatingcells,butismaintainedatalowlevelinthebrainbecauseitmakescellspronetopolyQaggregation.Herewefoundthatneuronalcell-specificbasallevelofVRK2isregulatednotbytranscriptionalregulationbutbypost-transcriptionalregulation. HnRNPQspecificallybindsto3’UTRofVrk2mRNAinneuronalcellsandreduceditsmRNAstability.WereportadramaticdecreaseinCCT4levelbyreducinghnRNPQ,whichcontributetoincreaseinpolyQaggregation.Thus,ourresultsdemonstratethatthelevelofbrainhnRNPQcontributestoHDprogressionbyregulatingVrk2mRNAstabilityandopennewnobleprognosticmarkerofHD.
- Article Type
- Conference
- Citation
- KSBMB International Conference 2017, 2017-05-18
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- 김경태KIM, KYONG TAI
- Dept of Life Sciences