An Abundant Evolutionarily Conserved CSB-PiggyBac Fusion Protein Expressed in Cockayne Syndrome 英文参考文献.docVIP

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An Abundant Evolutionarily Conserved CSB-PiggyBac Fusion Protein Expressed in Cockayne Syndrome 英文参考文献.doc

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An Abundant Evolutionarily Conserved CSB-PiggyBac Fusion Protein Expressed in Cockayne Syndrome 英文参考文献

AnAbundantEvolutionarilyConservedCSB-PiggyBac FusionProteinExpressedinCockayneSyndrome JohnC.Newman1,ArnoldD.Bailey1,Hua-YingFan2,ThomasPavelitz1,AlanM.Weiner1* 1DepartmentofBiochemistry,SchoolofMedicine,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica, 2FoxChaseCancerCenter,Philadelphia, Pennsylvania,UnitedStatesofAmerica Abstract Cockaynesyndrome(CS)isadevastatingprogeriamostoftencausedbymutationsintheCSBgeneencodingaSWI/SNF familychromatinremodelingprotein.AlthoughallCSBmutationsthatcauseCSarerecessive,thecompleteabsenceofCSB proteindoesnotcauseCS.Inaddition,mostCSBmutationsarelocatedbeyondexon5andarethoughttogenerateonlyC- terminallytruncatedproteinfragments.WenowshowthatadomesticatedPiggyBac-liketransposonPGBD3,residingwithin intron 5 of the CSB gene, functions as an alternative 39 terminal exon. The alternatively spliced mRNA encodes a novel chimericproteininwhichCSBexons1–5arejoinedinframetothePiggyBactransposase.TheresultingCSB-transposase fusionproteinisasabundantasCSBproteinitselfinavarietyofhumancelllines,andcontinuestobeexpressedbyprimary CScellsinwhichfunctionalCSBislostduetomutationsbeyondexon5.TheCSB-transposasefusionproteinhasbeenhighly conserved for at least 43 Myr since the divergence of humans and marmoset, and appears to be subject to selective pressure. The human genome contains over 600 nonautonomous PGBD3-related MER85 elements that were dispersed whenthePGBD3 transposase waslastactiveat least37Mya. ManyoftheseMER85 elementsareassociated withgenes which are involved in neuronal development, and are known to be regulated by CSB. We speculate that the CSB- transposasefusionproteinhasbeenconservedforhostantitransposondefense,ortomodulategeneregulationbyMER85 elements,butmaycauseCSintheabsenceoffunctionalCSBprotein. Citation: Newman JC, Bailey AD, Fan H-Y, Pavelitz T, Weiner AM (2008) An Abundant Evolutionarily Conserved CSB-PiggyBac Fusion Protein Expressed in CockayneSyndrome.PLoSGenet4(3):e1000031.doi:10.1371/journal