Phosphorylation of Arabidopsis eIF4E and eIFiso4E by SnRK1 inhibits translation
Phosphorylation of Arabidopsis eIF4E and eIFiso4E by SnRK1 inhibits translation
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DOI：
10.1111/febs.14935
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发表时间：
2019-10-01
期刊：
影响因子：
5.4
通讯作者：
Bisaro, David M.
中科院分区：
文献类型：
--
作者：
Bruns, Aaron N.;Li, Sizhun;Bisaro, David M.
蛋白质合成的调节对于维持细胞内稳态是至关重要的。在哺乳动物系统中，翻译调控网络已被阐明相当详细。然而，在植物中，调节通过不同的机制发生，这些机制在很大程度上仍然是难以捉摸的。在这项研究中，我们提出的证据表明，拟南芥能量传感激酶SnRK1，哺乳动物AMP激活激酶和酵母蔗糖非发酵1（SNF1）的同源物，抑制翻译磷酸化帽结合蛋白eIF4E和eIFiso4E。我们确定eIF4E和eIFiso4E含有两个高度保守的SnRK1共有靶位点，并且两者都与SnRK1在体内相互作用。然后，我们证明，SnRK1磷酸化抑制拟南芥eIF4E和eIFiso4E的能力，以补充缺乏内源性eIF4E的酵母菌株，抑制与抑制多核糖体形成。最后，我们表明，SnRK1在烟草本氏植物中的过度表达减少了多核糖体的形成，这种效果可以抵消瞬时表达的eIF4E或突变体eIF4E含有非磷酸化SnRK1靶残基，但不是由磷酸模拟eIF4E。总之，这些研究阐明了一种新的和直接的途径，在植物细胞中的翻译控制。鉴于之前的发现SnRK1调节先天抗病毒防御并被双生病毒致病因子抑制，我们推测帽结合蛋白的磷酸化可能是耐药机制的一个组成部分。
Regulation of protein synthesis is critical for maintaining cellular homeostasis. In mammalian systems, translational regulatory networks have been elucidated in considerable detail. In plants, however, regulation occurs through different mechanisms that remain largely elusive. In this study, we present evidence that the Arabidopsis thaliana energy sensing kinase SnRK1, a homologue of mammalian AMP-activated kinase and yeast sucrose non-fermenting 1 (SNF1), inhibits translation by phosphorylating the cap binding proteins eIF4E and eIFiso4E. We establish that eIF4E and eIFiso4E contain two deeply conserved SnRK1 consensus target sites and that both interact with SnRK1 in vivo. We then demonstrate that SnRK1 phosphorylation inhibits the ability of Arabidopsis eIF4E and eIFiso4E to complement a yeast strain lacking endogenous eIF4E, and that inhibition correlates with repression of polysome formation. Finally, we show that SnRK1 over-expression in Nicotiana benthamiana plants reduces polysome formation, and that this effect can be counteracted by transient expression of eIF4E or mutant eIF4E containing non-phosphorylatable SnRK1 target residues, but not by a phosphomimic eIF4E. Together, these studies elucidate a novel and direct pathway for translational control in plant cells. In light of previous findings that SnRK1 conditions an innate antiviral defense and is inhibited by geminivirus pathogenicity factors, we speculate that phosphorylation of cap binding proteins may be a component of the resistance mechanism.