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Systematic quantitative analysis of ribosome inventory during nutrient stress
Nature ( IF 64.8 ) Pub Date : 2020-07-01 , DOI: 10.1038/s41586-020-2446-y
Heeseon An 1 , Alban Ordureau 1 , Maria Körner 1, 2 , Joao A Paulo 1 , J Wade Harper 1
Affiliation  

Mammalian cells reorganize their proteomes in response to nutrient stress through translational suppression and degradative mechanisms using the proteasome and autophagy systems 1 , 2 . Ribosomes are central targets of this response, as they are responsible for translation and subject to lysosomal turnover during nutrient stress 3 – 5 . The abundance of ribosomal (r)-proteins (around 6% of the proteome; 10 7 copies per cell) 6 , 7 and their high arginine and lysine content has led to the hypothesis that they are selectively used as a source of basic amino acids during nutrient stress through autophagy 4 , 7 . However, the relative contributions of translational and degradative mechanisms to the control of r-protein abundance during acute stress responses is poorly understood, as is the extent to which r-proteins are used to generate amino acids when specific building blocks are limited 7 . Here, we integrate quantitative global translatome and degradome proteomics 8 with genetically encoded Ribo–Keima 5 and Ribo–Halo reporters to interrogate r-protein homeostasis with and without active autophagy. In conditions of acute nutrient stress, cells strongly suppress the translation of r-proteins, but, notably, r-protein degradation occurs largely through non-autophagic pathways. Simultaneously, the decrease in r-protein abundance is compensated for by a reduced dilution of pre-existing ribosomes and a reduction in cell volume, thereby maintaining the density of ribosomes within single cells. Withdrawal of basic or hydrophobic amino acids induces translational repression without differential induction of ribophagy, indicating that ribophagy is not used to selectively produce basic amino acids during acute nutrient stress. We present a quantitative framework that describes the contributions of biosynthetic and degradative mechanisms to r-protein abundance and proteome remodelling in conditions of nutrient stress. During nutrient stress, ribosomal protein abundance is regulated primarily by translational and non-autophagic degradative mechanisms, but ribosome density per cell is largely maintained by reductions in cell volume and rates of cell division.

中文翻译:

营养胁迫下核糖体库存的系统定量分析

哺乳动物细胞通过使用蛋白酶体和自噬系统 1, 2 的翻译抑制和降解机制,重新组织蛋白质组以应对营养压力。核糖体是这种反应的核心目标,因为它们负责翻译并在营养压力 3-5 期间受到溶酶体更新。丰富的核糖体 (r)-蛋白质(约占蛋白质组的 6%;每个细胞 10 7 个拷贝)6 , 7 及其高精氨酸和赖氨酸含量导致假设它们被选择性用作碱性氨基酸的来源在通过自噬 4 、 7 的营养压力。然而,在急性应激反应期间,翻译和降解机制对控制 r 蛋白丰度的相对贡献知之甚少,当特定构建块受到限制 7 时,r-蛋白质用于生成氨基酸的程度也是如此。在这里,我们将定量的全局翻译组和降解组蛋白质组学 8 与遗传编码的 Ribo-Keima 5 和 Ribo-Halo 报告基因相结合,以询问有和没有主动自噬的 r 蛋白稳态。在急性营养应激条件下,细胞强烈抑制 r-蛋白的翻译,但值得注意的是,r-蛋白降解主要通过非自噬途径发生。同时,r-蛋白丰度的降低通过减少预先存在的核糖体的稀释和细胞体积的减少来补偿,从而保持单细胞内核糖体的密度。碱性或疏水性氨基酸的撤回诱导翻译抑制,而不会引起核吞噬作用的差异诱导,表明在急性营养胁迫期间,不会使用核糖体来选择性地产生碱性氨基酸。我们提出了一个定量框架,描述了生物合成和降解机制对营养胁迫条件下 r 蛋白丰度和蛋白质组重塑的贡献。在营养应激期间,核糖体蛋白丰度主要受翻译和非自噬降解机制的调节,但每个细胞的核糖体密度主要通过细胞体积和细胞分裂率的减少来维持。
更新日期:2020-07-01
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