Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow, United Kingdom.
PLoS One. 2024 Oct 14;19(10):e0284234. doi: 10.1371/journal.pone.0284234. eCollection 2024.
The quantity of each protein in a cell only is only partially correlated with its gene transcription rate. Independent influences on protein synthesis levels include mRNA sequence motifs, amino acyl-tRNA synthesis levels, elongation factor action, and protein susceptibility to degradation. Here we report that the amino acid composition of a protein can also influence its expression level in two distinct ways. The nutritional classification of amino acids in animals reflects their potential for scarcity-essential amino acids (EAA) are reliant on dietary supply, non-essential amino acids (NEAA) from internal biosynthesis, and conditionally essential amino acids (CEAA) from both. Accessing public proteomic datasets, we demonstrate that a protein's CEAA sequence composition is inversely correlated with expression-a correlation enhanced during rapid cellular proliferation-suggesting CEAA availability can limit translation. Similarly, proteins with the most extreme compositions of EAA are generally reduced in abundance. These latter proteins participate in biological systems such as taste and food-seeking behaviour, oxidative phosphorylation, and chemokine function, and so linking their expression to EAA availability may act as a homeostatic response to malnutrition. Protein composition can also influence general human phenotypes and disease susceptibility: stature proteins are enriched in CEAAs, and a curated dataset of over 700 cancer proteins is significantly under-represented in EAAs. We also show that individual amino acids can influence protein expression across all kingdoms of life and that this effect appears to be rooted in the unchanging structural and mRNA encoding features of each amino acid. Species-specific environmental survival pathways are shown to be enriched in proteins with individual amino acid compositions favouring higher expression. These two forms of amino acid-driven protein expression regulation promise new insights into systems biology, evolutionary studies, experimental research design, and public health intervention.
细胞中每种蛋白质的数量与其基因转录率只有部分相关。独立影响蛋白质合成水平的因素包括 mRNA 序列基序、氨酰-tRNA 合成水平、延伸因子作用以及蛋白质对降解的敏感性。在这里，我们报告称，蛋白质的氨基酸组成也可以以两种不同的方式影响其表达水平。动物的氨基酸营养分类反映了它们的稀缺性——必需氨基酸（EAA）依赖于饮食供应，非必需氨基酸（NEAA）来自内部生物合成，条件必需氨基酸（CEAA）来自两者。我们利用公共蛋白质组学数据集证明，蛋白质的 CEAA 序列组成与表达呈负相关——这种相关性在细胞快速增殖期间增强——表明 CEAA 的可用性可能限制翻译。同样，具有最极端 EAA 组成的蛋白质通常丰度降低。这些后者蛋白质参与味觉和觅食行为、氧化磷酸化和趋化因子功能等生物学系统，因此将它们的表达与 EAA 的可用性联系起来可能是对营养不良的一种体内平衡反应。蛋白质组成还可以影响人类的一般表型和疾病易感性：身高蛋白质富含 CEAAs，超过 700 种癌症蛋白质的经过精心整理的数据集在 EAA 中显著不足。我们还表明，单个氨基酸可以影响所有生命领域的蛋白质表达，并且这种影响似乎根植于每个氨基酸不变的结构和 mRNA 编码特征中。具有个别氨基酸组成有利于更高表达的蛋白质，其物种特异性环境生存途径富集。这两种形式的氨基酸驱动的蛋白质表达调控有望为系统生物学、进化研究、实验研究设计和公共卫生干预提供新的见解。
