Dietary restriction (DR) increases life span through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of Caenorhabditis elegans subjected to DR. Transcription of muscle regulatory and structural genes increased, whereas increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of posttranscriptional regulation identified putative roles for RNA-binding proteins, RNA editing, miRNA, alternative splicing, and nonsense-mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate life span. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally down-regulated genes. Furthermore, 3' UTR editing and intron retention increase under DR and correlate with diminished translation, whereas trans-spliced genes are refractory to reduced translation efficiency compared with messages with the native 5' UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense-mediated decay targets, are required for increased life span under DR.

中文翻译：

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饮食限制诱导长寿基因的转录后调控。

饮食限制 (DR) 通过基因表达的适应性变化来延长寿命。为了更多地了解这些变化，我们分析了秀丽隐杆线虫的转录组和翻译组受到DR。肌肉调节和结构基因的转录增加，而氨基酸代谢和神经肽信号基因的表达增加则控制在翻译水平。转录后调控的评估确定了 RNA 结合蛋白、RNA 编辑、miRNA、可变剪接和无义介导的营养限制衰变的假定作用。使用 RNA 干扰，我们发现了几个调节寿命的差异表达基因。我们还发现了翻译调控的补偿作用，它抵消了大部分转录下调基因的抑制表达。此外，3' UTR 编辑和内含子保留在 DR 下增加，并与翻译减少相关，而与具有天然 5' UTR 的信息相比，反式剪接基因难以降低翻译效率。最后，我们发现smg-6和smg-7是控制无义介导的衰变目标选择和周转的基因，它们是 DR 下延长寿命所必需的。