gadd45a is an rna binding protein and is localized in nuclear specklesgadd45a rna结合蛋白,核斑点的本地化.pdfVIP
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gadd45a is an rna binding protein and is localized in nuclear specklesgadd45a rna结合蛋白,核斑点的本地化
Gadd45a Is an RNA Binding Protein and Is Localized in
Nuclear Speckles
1 2 ¨ 1 2
Yuliya A. Sytnikova , Andriy V. Kubarenko , Andrea Schafer , Alexander N. R. Weber , Christof
Niehrs1,3*
1 Division of Molecular Embryology, DKFZ-ZMBH Alliance, Krebsforschungszentrum, Heidelberg, Germany, 2 Division of Toll-like Receptors and Cancer, Deutsches
Krebsforschungszentrum, Heidelberg, Germany, 3 Institute of Molecular Biology (IMB), Mainz, Germany
Abstract
Background: The Gadd45 proteins play important roles in growth control, maintenance of genomic stability, DNA repair,
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
ribosomal proteins, which raises the question if they may interact directly with nucleic acids.
Principal Findings: Here we show that Gadd45a binds RNA but not single- or double stranded DNA or methylated DNA in
vitro. Sucrose density gradient centrifugation experiments demonstrate that Gadd45a is present in high molecular weight
particles, which are RNase sensitive. Gadd45a displays RNase-sensitive colocalization in nuclear speckles with the RNA
helicase p68 and the RNA binding protein SC35. A K45A point mutation defective in RNA binding was still active in DNA
demethylation. This suggests that RNA binding is not absolutely essential for demethylation of an artificial substrate. A point
mutation at G39 impared RNA binding, nuclear speckle localization and DNA demethylation, emphasizing its relevance for
Gadd45a function.
Significance: The results implicate RNA in Gadd45a function and suggest that
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