小柯机器人

美国哈佛医学院J. Wade Harper研究小组的一项最新研究探索了营养胁迫条件下核糖体库的系统定量分析。相关论文于2020年7月1日在线发表在《自然》杂志上。

研究人员将定量翻译组和降解组蛋白质组学与遗传编码的Ribo–Keima和Ribo–Halo报告基因整合在一起，以研究在有或没有主动自噬情况下r蛋白的稳态。在急性营养胁迫条件下，细胞会强烈抑制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-蛋白质丰度的降低可以通过减少预先存在核糖体的浓度以及减少细胞体积来弥补，从而保持单个细胞内核糖体的密度。

减少碱性或疏水性氨基酸可诱导翻译抑制，而不会引起核糖体自噬的差异诱导，这表明在急性营养胁迫期间，核糖体自噬未用于选择性地产生碱性氨基酸。该研究提供了一个定量机制，即在营养胁迫条件下，生物合成和降解机制对r蛋白丰度和蛋白质组重塑的影响。

据介绍，哺乳动物细胞利用蛋白酶体和自噬系统的翻译抑制和降解机制来响应营养胁迫而重组其蛋白质组。核糖体是该反应的核心组分，因为它们负责翻译并在营养胁迫时调控溶酶体更新。核糖体（r）蛋白的丰富性（大约占蛋白质组的6％；每个细胞107个拷贝）及其高精氨酸和赖氨酸含量产生了这样一个假设，即在营养胁迫时它们通过自噬被选择性地用作碱性氨基酸的来源。但是，人们对在急性应激反应时翻译和降解机制对r蛋白丰度调控的相对贡献知之甚少，当特定营养成分受限制时，r蛋白也很少被用于生成氨基酸。

附：英文原文

Title: Systematic quantitative analysis of ribosome inventory during nutrient stress

Author: Heeseon An, Alban Ordureau, Maria Krner, Joao A. Paulo, J. Wade Harper

Issue&Volume: 2020-07-01

Abstract: Mammalian cells reorganize their proteomes in response to nutrient stress through translational suppression and degradative mechanisms using the proteasome and autophagy systems1,2. Ribosomes are central targets of this response, as they are responsible for translation and subject to lysosomal turnover during nutrient stress3,4,5. The abundance of ribosomal (r)-proteins (around 6% of the proteome; 107 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 autophagy4,7. 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 limited7. Here, we integrate quantitative global translatome and degradome proteomics8 with genetically encoded Ribo–Keima5 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.

DOI: 10.1038/s41586-020-2446-y

Source: https://www.nature.com/articles/s41586-020-2446-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html