Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2α phosphorylation
Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2α phosphorylation
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DOI：
10.1091/mbc.e06-04-0318
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发表时间：
2006-10-01
影响因子：
3.3
通讯作者：
Pelletier, Jerry
中科院分区：
文献类型：
--
作者：
Mazroui, Rachid;Sukarieh, Rami;Pelletier, Jerry
被称为应激颗粒（SG）的细胞质聚集体是细胞应激的结果，包含停滞的翻译前起始复合物。这些病灶被认为是细胞应激反应期间mRNA储存或分类的位点。SG的形成需要诱导真核起始因子（eIF）2 α磷酸化。在此，我们研究了其他起始因子在这一过程中的潜在作用，并证明干扰eIF4A活性（翻译起始的核糖体募集阶段所需的RNA解旋酶）诱导SG形成，并且该事件不依赖于eIF2 α磷酸化。我们还表明，抑制eIF4A活性不会损害eIF2 α在应激条件下被磷酸化的能力。此外，我们观察到脊髓灰质炎病毒感染后抑制帽依赖性翻译的SG组装。我们提出，SG建模可以发生通过eIF2 α磷酸化依赖性和非依赖性途径，目标翻译起始。
Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (elF)2 alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2 alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2 alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2 alpha phosphorylation-dependent and -independent pathways that target translation initiation.