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首页> 外文期刊>Cell metabolism >Translational Tolerance of Mitochondrial Genes to Metabolic Energy Stress Involves TISU and eIF1-eIF4GI Cooperation in Start Codon Selection
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Translational Tolerance of Mitochondrial Genes to Metabolic Energy Stress Involves TISU and eIF1-eIF4GI Cooperation in Start Codon Selection

机译：线粒体基因对代谢能应激的翻译耐受性涉及起始密码子选择中的TISU和eIF1-eIF4GI合作。

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Protein synthesis is a major energy-consuming process, which is rapidly repressed upon energy stress by AMPK. How energy deficiency affects translation of mRNAs that cope with the stress response is poorly understood. We found that mitochondrial genes remain translationally active upon energy deprivation. Surprisingly, inhibition of translation is partially retained in AMPKa1/AMPKa2 knockout cells. Mitochondrial mRNAs are enriched with TISU, a translation initiator of short 5' UTR, which confers resistance specifically to energy stress. Purified 48S preinitiation complex is sufficient for initiation via TISU AUG, when preceded by a short 50 UTR. eIF1 stimulates TISU but inhibits non-TISU-directed initiation. Remarkably, eIF4GI shares this activity and also interacts with eIF1. Furthermore, eIF4F is released upon 48S formation on TISU. These findings describe a specialized translation tolerance mechanism enabling continuous translation of TISU genes under energy stress and reveal that a key step in start codon selection of short 5' UTR is eIF4F release.
机译：蛋白质合成是主要的能量消耗过程，AMPK在能量压力下会迅速抑制蛋白质合成。能量缺乏如何影响应对压力反应的mRNA的翻译知之甚少。我们发现线粒体基因在能量剥夺后仍保持翻译活性。令人惊讶地，翻译的抑制部分保留在AMPKa1 / AMPKa2敲除细胞中。线粒体mRNA富含TISU（短5'UTR的翻译起始物），可特异性赋予对能量压力的抗性。纯化的48S预启动复合物足以在短时50 UTR之后通过TISU AUG启动。 eIF1刺激TISU，但抑制非TISU定向的启动。值得注意的是，eIF4GI共享此活动，并且还与eIF1交互。此外，eIF4F在TISU上形成48S后释放。这些发现描述了一种特殊的翻译耐受机制，可在能量压力下连续翻译TISU基因，并揭示了在短5'UTR起始密码子选择中的关键步骤是eIF4F的释放。

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