HuR controls mitochondrial morphology through the regulation of BclxL translation
HuR controls mitochondrial morphology through the regulation of BclxL translation
复制标题
DOI：
10.4161/trla.23980
复制
发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Holcik, Martin
中科院分区：
文献类型：
--
作者：
Durie, Danielle;Hatzoglou, Maria;Holcik, Martin
Bcl(xL) 是一个关键的促存活因子，除了控制线粒体膜通透性之外，还调节线粒体网络动态。 Bcl(xL) 的表达在转录、剪接和选择性翻译水平上受到调节。在这项研究中，我们发现 RNA 结合蛋白 HuR（已知可协调抗凋亡细胞程序）可作为 Bcl(xL) 的翻译阻遏蛋白发挥作用。我们发现 HuR 直接与 Bcl(xL) 的 5' UTR 结合，并通过抑制其内部核糖体进入位点 (IRES) 来抑制 Bcl(xL) 翻译。 HuR 水平的降低会导致 Bcl(xL) 翻译的去抑制以及随后线粒体网络的重排。我们的结果将 Bcl(xL) 置于 HuR 调节的操纵子中，并进一步深入了解 HuR 对细胞应激反应的调节。
Bcl(xL) is a key prosurvival factor that in addition to controlling mitochondrial membrane permeability regulates mitochondrial network dynamics. The expression of Bcl(xL) is regulated at the level of transcription, splicing and selective translation. In this study, we show that the RNA-binding protein HuR, which is known to orchestrate an anti-apoptotic cellular program, functions as a translational repressor of Bcl(xL). We show that HuR binds directly to the 5' UTR of Bcl(xL), and represses Bcl(xL) translation through the inhibition of its internal ribosome entry site (IRES). Reduction of HuR levels leads to the derepression of Bcl(xL) translation and subsequent rearrangement of the mitochondrial network. Our results place Bcl(xL) into the HuR-regulated operon and provide further insight into the regulation of cellular stress response by HuR.