Oxygen level regulates N-terminal translation elongation of selected proteins through deoxyhypusine hydroxylation.
Oxygen level regulates N-terminal translation elongation of selected proteins through deoxyhypusine hydroxylation.
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DOI：
10.1016/j.celrep.2022.110855
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发表时间：
2022-05-24
期刊：
影响因子：
8.8
通讯作者：
Lin, Hening
中科院分区：
文献类型：
--
作者：
Zhang, Yugang;Su, Dan;Zhu, Julia;Wang, Miao;Zhang, Yandong;Fu, Qin;Zhang, Sheng;Lin, Hening
Hypusine是真核生物翻译起始因子5A （eIF5A）的翻译后修饰。hypusine生物合成的最后一步，脱氧hypusine羟基化，是一个依赖氧的反应。在这里，我们表明脱氧hypusine羟化酶Lia1的缺失通过翻译下调呼吸途径中选择的蛋白质来损害酵母呼吸。翻译抑制，由于缺乏脱氧hypusine羟基化，主要影响蛋白质的N端翻译，不依赖于脯氨酸残基的存在，但可能依赖于N端新生肽和核糖体肽出口通道之间的相互作用。蛋白质组学和生化研究表明，Lia1缺失减少了参与线粒体呼吸、氧化应激反应和蛋白质折叠的蛋白质的n端翻译。我们的工作通过考虑翻译后修饰对底物的要求，揭示了hypusine修饰的功能，强调了蛋白质N端翻译的独特挑战，并揭示了真核细胞中的氧感应机制。细胞必须根据氧气水平调节新陈代谢。Zhang等人发现氧气调节酵母中翻译因子eIF5A的羟基化。羟基化作用以不依赖脯氨酸的方式促进许多蛋白质的N端翻译，这些蛋白质对细胞在氧气存在下的生存至关重要。
Hypusine is a post-translational modification on eukaryotic translation initiation factor 5A (eIF5A). The last step of hypusine biosynthesis, deoxyhypusine hydroxylation, is an oxygen-dependent reaction. Here we show that deletion of the deoxyhypusine hydroxylase Lia1 compromises yeast respiration through translation downregulation of selected proteins in the respiration pathway. The translation suppression, because of the lack of deoxyhypusine hydroxylation, mainly affects translation of the N termini of the proteins, independent of the presence of proline residues but likely dependent on the interaction between the N-terminal nascent peptide and the ribosomal peptide exit tunnel. Proteomics and biochemical studies reveal that Lia1 deletion decreases N-terminal translation of proteins involved in mitochondrial respiration, oxidative stress response, and protein folding. Our work uncovers functions of the hypusine modification by considering the substrate requirement of the post-translational modification, highlights the unique challenges of translating the N termini of proteins, and reveals an oxygen-sensing mechanism in eukaryotic cells. Cells have to regulate their metabolism in response to oxygen levels. Zhang et al. find that oxygen regulates hydroxylation of translation factor eIF5A in yeast. Hydroxylation promotes translation of the N termini of many proteins essential for cell survival in the presence of oxygen in a proline-independent manner.
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