Antiapoptotic function of RNA-binding protein HuR effected through prothymosin α
Antiapoptotic function of RNA-binding protein HuR effected through prothymosin α
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DOI：
10.1038/sj.emboj.7600661
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发表时间：
2005-05-18
期刊：
影响因子：
11.4
通讯作者：
Gorospe, M
中科院分区：
文献类型：
--
作者：
Lal, A;Kawai, T;Gorospe, M
我们报告了 RNA 结合蛋白 HuR 的抗凋亡作用，HuR 是靶转录物转录后命运的关键调节因子。与 HuR 复合的最突出的 mRNA 是编码前胸腺素 a (ProT α)（一种凋亡体抑制剂）的 mRNA。在 HeLa 细胞中，用凋亡刺激紫外线 (UVC) 处理会触发 ProT α mRNA 动员到细胞质和较重的多聚体上，其中其与 HuR 的关联显着增加。对嵌合 ProT α mRNA 的分析直接表明 HuR 参与调节 ProT α 的产生：在 HuR 过表达的细胞中，ProT α 翻译和细胞质浓度增加，而在通过 RNA 干扰降低 HuR 水平的细胞中，ProT α 翻译和细胞质浓度下降。重要的是，HuR 产生的抗凋亡影响很大程度上依赖于 ProT α 表达，因为使用阻断 ProT α 翻译的寡聚物消除了 HuR 的保护作用。总之，我们的数据支持一种调控方案，即 HuR 结合 ProT α mRNA，提高其细胞质丰度和翻译，从而引发抗凋亡程序。
We report the antiapoptotic effect of RNA-binding protein HuR, a critical regulator of the post-transcriptional fate of target transcripts. Among the most prominent mRNAs complexing with HuR is that encoding prothymosin a (ProT alpha), an inhibitor of the apoptosome. In HeLa cells, treatment with the apoptotic stimulus ultraviolet light (UVC) triggered the mobilization of ProT alpha mRNA to the cytoplasm and onto heavier polysomes, where its association with HuR increased dramatically. Analysis of a chimeric ProT alpha mRNA directly implicated HuR in regulating ProT alpha production: ProT alpha translation and cytoplasmic concentration increased in HuR-overexpressing cells and declined in cells in which HuR levels were lowered by RNA interference. Importantly, the antiapoptotic influence engendered by HuR was vitally dependent on ProT alpha expression, since use of oligomers that blocked ProT alpha translation abrogated the protective effect of HuR. Together, our data support a regulatory scheme whereby HuR binds the ProT alpha mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.