Gadd45a is an RNA binding protein and is localized in nuclear speckles.
Gadd45a is an RNA binding protein and is localized in nuclear speckles.
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DOI：
10.1371/journal.pone.0014500
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发表时间：
2011-01-07
期刊：
影响因子：
3.7
通讯作者：
Niehrs C
中科院分区：
文献类型：
--
作者：
Sytnikova YA;Kubarenko AV;Schäfer A;Weber AN;Niehrs C
Gadd 45蛋白在生长控制、维持基因组稳定性、DNA修复和凋亡中起重要作用。最近，Gadd 45蛋白还通过促进活性DNA去甲基化参与表观遗传基因调控。Gadd 45蛋白与核糖体蛋白的L7 Ae/L30 e/S12 e RNA结合超家族具有序列同源性，这提出了它们是否可以直接与核酸相互作用的问题。在这里，我们表明，Gadd 45 a结合RNA，但不单链或双链DNA或甲基化的DNA在体外。蔗糖密度梯度离心实验证明Gadd 45 a存在于高分子量颗粒中，其是RNA酶敏感的。Gadd 45 a与RNA解旋酶p68和RNA结合蛋白SC 35在核斑点中显示RNA酶敏感性共定位。RNA结合缺陷的K45 A点突变在DNA去甲基化中仍然活跃。这表明RNA结合对于人工底物的去甲基化不是绝对必要的。在G39免疫RNA结合、核斑点定位和DNA去甲基化处的点突变，强调其与Gadd 45 a功能的相关性。结果表明RNA参与了Gadd 45 a的功能，并提示Gadd 45 a与核糖核蛋白颗粒相关。
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. 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. The results implicate RNA in Gadd45a function and suggest that Gadd45a is associated with a ribonucleoprotein particle.
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影响因子：
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作者：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1083/jcb.106.5.1419
发表时间：
1988-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dreyfuss G;Philipson L;Mattaj IW
通讯作者：
Mattaj IW