Institut de biologie moléculaire des plantes UPR2357 du CNRS, Université de Strasbourg, Strasbourg, France.
Institute of Protein Research of the Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
Cell Rep. 2023 Aug 29;42(8):112892. doi: 10.1016/j.celrep.2023.112892. Epub 2023 Jul 29.
Mammalian/mechanistic target of rapamycin (mTOR) regulates global protein synthesis through inactivation of eIF4E-binding proteins (m4E-BPs) in response to nutrient and energy availability. Until now, 4E-BPs have been considered as metazoan inventions, and how target of rapamycin (TOR) controls cap-dependent translation initiation in plants remains obscure. Here, we present short unstructured 4E-BP-like Arabidopsis proteins (4EBP1/4EBP2) that are non-homologous to m4E-BPs except for the eIF4E-binding motif and TOR phosphorylation sites. Unphosphorylated 4EBPs exhibit strong affinity toward eIF4Es and can inhibit formation of the cap-binding complex. Upon TOR activation, 4EBPs are phosphorylated, probably when bound directly to TOR, and likely relocated to ribosomes. 4EBPs can suppress a distinct set of mRNAs; 4EBP2 predominantly inhibits translation of core cell-cycle regulators CycB1;1 and CycD1;1, whereas 4EBP1 interferes with chlorophyll biosynthesis. Accordingly, 4EBP2 overexpression halts early seedling development, which is overcome by induction of Glc/Suc-TOR signaling. Thus, TOR regulates cap-dependent translation initiation by inactivating atypical 4EBPs in plants.
哺乳动物/雷帕霉素靶蛋白 (mTOR) 通过响应营养和能量可用性使 eIF4E 结合蛋白 (m4E-BPs) 失活来调节全球蛋白质合成。直到现在，4E-BPs 一直被认为是后生动物的发明，而雷帕霉素靶蛋白 (TOR) 如何在植物中控制帽依赖性翻译起始仍然不清楚。在这里，我们提出了短的非结构化拟南芥 4E-BP 样蛋白 (4EBP1/4EBP2)，除了 eIF4E 结合基序和 TOR 磷酸化位点外，它们与 m4E-BPs 没有同源性。未磷酸化的 4EBPs 对 eIF4Es 表现出很强的亲和力，并能抑制帽结合复合物的形成。在 TOR 激活后，4EBPs 被磷酸化，可能是在直接与 TOR 结合时被磷酸化，并且可能被重新定位到核糖体上。4EBPs 可以抑制一组独特的 mRNA；4EBP2 主要抑制细胞周期核心调节因子 CycB1;1 和 CycD1;1 的翻译，而 4EBP1 干扰叶绿素生物合成。因此，4EBP2 的过表达会阻止早期幼苗的发育，而 Glc/Suc-TOR 信号的诱导可以克服这一问题。因此，TOR 通过使植物中非典型 4EBPs 失活来调节帽依赖性翻译起始。
