Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes
Production of Protein-Complex Components Is Stoichiometric and Lacks General Feedback Regulation in Eukaryotes
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DOI：
10.1016/j.cels.2018.11.003
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发表时间：
2018-12-26
期刊：
影响因子：
9.3
通讯作者：
Li, Gene-Wei
中科院分区：
文献类型：
--
作者：
Taggart, James C.;Li, Gene-Wei
多蛋白复合物的成分需要在相互之间明确定义的水平上。然而，尚不清楚真核细胞是否通常产生精确数量的亚基，还是依靠降解来减轻不精确的生产。在这里，我们使用核糖体分析定量了单细胞和多细胞真核生物中多蛋白复合物的生产速率。通过解决在真核生物中大部分核糖体足迹和扭曲定量准确性的读图歧义，我们发现多蛋白复合物的专门成分是按其化学计量比例产生的，这表明它们的丰度已经在合成水平上精确调整。通过系统地询问基因剂量变化对出芽酵母的影响，我们发现普遍缺乏保护亚基合成正常精确速率的负反馈调节。这些结果揭示了蛋白质组稳态的核心原理，并突出了在中心法则的每一步向定量控制的进化。
Constituents of multiprotein complexes are required at well-defined levels relative to each other. However, it remains unknown whether eukaryotic cells typically produce precise amounts of subunits, or instead rely on degradation to mitigate imprecise production. Here, we quantified the production rates of multiprotein complexes in unicellular and multicellular eukaryotes using ribosome profiling. By resolving read-mapping ambiguities, which occur for a large fraction of ribosome footprints and distort quantitation accuracy in eukaryotes, we found that obligate components of multiprotein complexes are produced in proportion to their stoichiometry, indicating that their abundances are already precisely tuned at the synthesis level. By systematically interrogating the impact of gene dosage variations in budding yeast, we found a general lack of negative feedback regulation protecting the normally precise rates of subunit synthesis. These results reveal a core principle of proteome homeostasis and highlight the evolution toward quantitative control at every step in the central dogma.