Howard Hughes Medical Institute, Duke University, Durham, NC 27708, USA; Department of Biology, Duke University, Durham, NC 27708, USA.
Howard Hughes Medical Institute, Duke University, Durham, NC 27708, USA; Department of Biology, Duke University, Durham, NC 27708, USA.
Cell. 2022 Aug 18;185(17):3186-3200.e17. doi: 10.1016/j.cell.2022.06.037. Epub 2022 Jul 30.
Upon stress, eukaryotes typically reprogram their translatome through GCN2-mediated phosphorylation of the eukaryotic translation initiation factor, eIF2α, to inhibit general translation initiation while selectively translating essential stress regulators. Unexpectedly, in plants, pattern-triggered immunity (PTI) and response to other environmental stresses occur independently of the GCN2/eIF2α pathway. Here, we show that while PTI induces mRNA decapping to inhibit general translation, defense mRNAs with a purine-rich element ("R-motif") are selectively translated using R-motif as an internal ribosome entry site (IRES). R-motif-dependent translation is executed by poly(A)-binding proteins (PABPs) through preferential association with the PTI-activating eIFiso4G over the repressive eIF4G. Phosphorylation by PTI regulators mitogen-activated protein kinase 3 and 6 (MPK3/6) inhibits eIF4G's activity while enhancing PABP binding to the R-motif and promoting eIFiso4G-mediated defense mRNA translation, establishing a link between PTI signaling and protein synthesis. Given its prevalence in both plants and animals, the PABP/R-motif translation initiation module may have a broader role in reprogramming the stress translatome.
在应激条件下，真核生物通常通过 GCN2 介导的真核翻译起始因子 eIF2α 的磷酸化来重新编程其翻译组，从而抑制一般翻译起始，同时选择性地翻译必需的应激调节剂。出乎意料的是，在植物中，模式触发免疫 (PTI) 和对其他环境应激的反应独立于 GCN2/eIF2α 途径发生。在这里，我们表明，虽然 PTI 诱导 mRNA 脱帽以抑制一般翻译，但富含嘌呤的元件 ("R 基序") 的防御 mRNA 被选择性地翻译，使用 R 基序作为内部核糖体进入位点 (IRES)。R 基序依赖性翻译是由聚(A)结合蛋白 (PABP) 通过与激活 PTI 的 eIFiso4G 优先结合而不是与抑制 eIF4G 结合来执行的。PTI 调节剂丝裂原激活蛋白激酶 3 和 6 (MPK3/6) 的磷酸化抑制 eIF4G 的活性，同时增强 PABP 与 R 基序的结合，并促进 eIFiso4G 介导的防御 mRNA 翻译，从而在 PTI 信号转导和蛋白质合成之间建立联系。鉴于其在植物和动物中普遍存在，PABP/R 基序翻译起始模块可能在重新编程应激翻译组方面具有更广泛的作用。
