Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Cell Metab. 2011 Jul 6;14(1):55-66. doi: 10.1016/j.cmet.2011.05.010.
Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.
降低蛋白质合成会减缓生长和发育速度，但可以延长成年寿命。我们证明，在饥饿和 dauer 状态下下调的真核翻译起始因子 4G (eIF4G) 的敲低导致线虫中与生长和长寿相关的基因的差异翻译。全基因组 mRNA 翻译状态分析表明，抑制 IFG-1（线虫 eIF4G 的同源物）导致核糖体加载和应激反应基因翻译的相对增加。当抑制 IFG-1 时，其中一些基因对于延长寿命是必需的。此外，IFG-1 抑制时某些 mRNA 的核糖体加载增加与 mRNA 长度增加相关。通过定量质谱分析检测到的蛋白质组变化支持了这种关联。我们的结果表明，IFG-1 通过调节特定 mRNA 的翻译来介导生长和体维持之间的拮抗作用，部分基于转录本长度。
