Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles 英文参考文献.docVIP

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Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles 英文参考文献.doc

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Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles 英文参考文献

Gadd45aIsanRNABindingProteinandIsLocalizedin NuclearSpeckles YuliyaA.Sytnikova1,AndriyV.Kubarenko2,AndreaScha¨fer1,AlexanderN.R.Weber2 ,Christof Niehrs1,3 * 1Division of Molecular Embryology, DKFZ-ZMBH Alliance, Krebsforschungszentrum, Heidelberg, Germany, 2Division of Toll-like Receptors and Cancer, Deutsches Krebsforschungszentrum,Heidelberg,Germany,3InstituteofMolecularBiology(IMB),Mainz,Germany Abstract Background:TheGadd45proteinsplayimportantrolesingrowthcontrol,maintenanceofgenomicstability,DNArepair, and apoptosis. Recently, Gadd45 proteins have also been implicated in epigenetic gene regulation by promoting active DNA demethylation. Gadd45 proteins have sequence homology with the L7Ae/L30e/S12e RNA binding superfamily of ribosomalproteins,whichraisesthequestioniftheymayinteractdirectlywithnucleicacids. PrincipalFindings:HereweshowthatGadd45abindsRNAbutnotsingle-ordoublestrandedDNAormethylatedDNAin vitro.SucrosedensitygradientcentrifugationexperimentsdemonstratethatGadd45aispresentinhighmolecularweight particles, which are RNase sensitive. Gadd45a displays RNase-sensitive colocalization in nuclear speckles with the RNA helicasep68andtheRNAbindingproteinSC35.AK45ApointmutationdefectiveinRNAbindingwasstillactiveinDNA demethylation.ThissuggeststhatRNAbindingisnotabsolutelyessentialfordemethylationofanartificialsubstrate.Apoint mutationatG39imparedRNAbinding,nuclearspecklelocalizationandDNAdemethylation,emphasizingitsrelevancefor Gadd45afunction. Significance: The results implicate RNA in Gadd45a function and suggest that Gadd45a is associated with a ribonucleoproteinparticle. Citation:SytnikovaYA,KubarenkoAV,Scha¨fer A,WeberANR,NiehrsC(2011)Gadd45aIsanRNABindingProteinandIsLocalizedinNuclearSpeckles.PLoS ONE6(1):e14500.doi:10.1371/journal.pone.0014500 Editor:Shuang-yongXu,NewEnglandBiolabs,Inc,UnitedStatesofAmerica ReceivedJune22,2010;AcceptedDecember9,2010;PublishedJanuary7,2011 Copyright: ? 2011 Sytnikova et al. This is an open-access article distribute