Recruitment of the RNA Helicase RHAU to Stress Granules via a Unique RNA-binding Domain
Recruitment of the RNA Helicase RHAU to Stress Granules via a Unique RNA-binding Domain
复制标题
DOI：
10.1074/jbc.m804857200
复制
发表时间：
2008-12-12
影响因子：
4.8
通讯作者：
Nagamine, Yoshikuni
中科院分区：
文献类型：
--
作者：
Chalupnikova, Katerina;Lattmann, Simon;Nagamine, Yoshikuni
为了应对环境压力，细胞的翻译机器被重新编程。大多数主动翻译的mRNA从多聚核糖体释放并被驱动到称为应激颗粒（SG）的特定细胞质病灶，其中蛋白质-RNA相互作用的动态变化决定mRNA的后续命运。在这里，我们表明DEAH盒RNA解旋酶RHAU是一种新型SG相关蛋白。尽管RHAU蛋白最初被鉴定为参与尿激酶型纤溶酶原激活物mRNA衰变的富含AU的元素相关蛋白，但尚不清楚RHAU是否可以直接与RNA相互作用。我们已经证明，RHAU物理相互作用与RNA在体外和体内通过一个新确定的N-末端RNA结合结构域，这被认为是必不可少的和足够的RHAU本地化的SG。我们还表明，RHAU的ATP酶活性在RNA相互作用和调节SGs中的蛋白质保留中起作用。因此，我们的研究结果表明，RHAU是在SGs中检测到的第四种RNA解旋酶，仅次于rck/p54，DDX 3和eIF 4A，并且其与SGs的关联是动态的，并由RHAU特异性RNA结合结构域介导。
In response to environmental stress, the translation machinery of cells is reprogrammed. The majority of actively translated mRNAs are released from polysomes and driven to specific cytoplasmic foci called stress granules (SGs) where dynamic changes in protein-RNA interaction determine the subsequent fate of mRNAs. Here we show that the DEAH box RNA helicase RHAU is a novel SG-associated protein. Although RHAU protein was originally identified as an AU-rich element-associated protein involved in urokinase-type plasminogen activator mRNA decay, it was not clear whether RHAU could directly interact with RNA. We have demonstrated that RHAU physically interacts with RNA in vitro and in vivo through a newly identified N-terminal RNA-binding domain, which was found to be both essential and sufficient for RHAU localization in SGs. We have also shown that the ATPase activity of RHAU plays a role in the RNA interaction and in the regulation of protein retention in SGs. Thus, our results show that RHAU is the fourth RNA helicase detected in SGs, after rck/p54, DDX3, and eIF4A, and that its association with SGs is dynamic and mediated by an RHAU-specific RNA-binding domain.