Mammalian Staufen 1 is recruited to stress granules and impairs their assembly
Mammalian Staufen 1 is recruited to stress granules and impairs their assembly
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DOI：
10.1242/jcs.038208
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发表时间：
2009-02-15
影响因子：
4
通讯作者：
Boccaccio, Graciela L.
中科院分区：
文献类型：
--
作者：
Gabriela Thomas, Maria;Martinez Tosar, Leandro J.;Boccaccio, Graciela L.
应激颗粒是在应激反应过程中瞬间形成的细胞质中的mRNA沉默焦点。应激颗粒含有流产的翻译起始复合体，并与翻译多聚体处于动态平衡状态。哺乳动物Staufen 1(Stau1)是一种普遍存在的与多聚体相关的双链RNA结合蛋白。在这里，我们表明，在内质网或氧化应激诱导时，Stau1被招募到应激颗粒中，以及在翻译起始阻滞剂诱导的应激颗粒中。我们发现，在细胞中形成的缺乏Stau1的应激颗粒耗尽了该分子，表明Stau1不是应激颗粒的重要组成部分。此外，Stau1基因敲除促进了应激诱导后应激颗粒的形成。相反，瞬时转导Stau1可抑制应激时应激颗粒的形成或药物启动的停止。Stau1的抑制能力被映射到分子的氨基末端半部分，这是一个已知与多聚体结合的区域。我们发现，在应激诱导过程中残留的多聚体部分在Stau1中得到了丰富，并且Stau1的过表达稳定了多聚体对抗应激的能力。我们认为，Stau1通过稳定多聚体参与应激的恢复，从而帮助应激颗粒的溶解。
Stress granules are cytoplasmic mRNA-silencing foci that form transiently during the stress response. Stress granules harbor abortive translation initiation complexes and are in dynamic equilibrium with translating polysomes. Mammalian Staufen 1 (Stau1) is a ubiquitous double-stranded RNA-binding protein associated with polysomes. Here, we show that Stau1 is recruited to stress granules upon induction of endoplasmic reticulum or oxidative stress as well in stress granules induced by translation initiation blockers. We found that stress granules lacking Stau1 formed in cells depleted of this molecule, indicating that Stau1 is not an essential component of stress granules. Moreover, Stau1 knockdown facilitated stress granule formation upon stress induction. Conversely, transient transfection of Stau1 impaired stress granule formation upon stress or pharmacological initiation arrest. The inhibitory capacity of Stau1 mapped to the amino-terminal half of the molecule, a region known to bind to polysomes. We found that the fraction of polysomes remaining upon stress induction was enriched in Stau1, and that Stau1 overexpression stabilized polysomes against stress. We propose that Stau1 is involved in recovery from stress by stabilizing polysomes, thus helping stress granule dissolution.