Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intracellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the ɛ-amine of lysines in their substrates by producing reactive aminoacyl adenylates. The K-AA marks can be removed by deacetylases, such as SIRT1 and SIRT3, employing the same mechanism as that involved in deacetylation. These dynamically regulated K-AAs transduce signals of their respective amino acids. Reversible leucylation on ras-related GTP-binding protein A/B regulates activity of the mammalian target of rapamycin complex 1. Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We discovered non-canonical functions of ARSs and revealed systematic and functional amino acid sensing and signal transduction networks.

中文翻译：

---

通过可逆的赖氨酸氨基酰化来传感和传递细胞内氨基酸信号。

氨基酸是已知的细胞信号传导和生理调节剂，但是如何在细胞内感测氨基酸尚不完全清楚。在这里，我们报告每个氨基酰基-tRNA合成酶（ARS）通过催化在其特定底物蛋白上形成赖氨酸氨基酰化（K-AA）来感知其同源氨基酸的充足性。在生理水平上，氨基酸通过产生反应性氨酰基腺苷酸来促进ARS与其底物结合，并在其底物中赖氨酸的α-胺上形成K-AA。可以通过脱乙酰基酶（例如SIRT1和SIRT3）去除K-AA标记，采用与脱乙酰基涉及的机制相同的机制。这些动态调节的K-AA转换其各自氨基酸的信号。与ras相关的GTP结合蛋白A / B的可逆性亮氨化作用可调节雷帕霉素复合物1的哺乳动物靶标的活性。对凋亡信号调节激酶1进行谷氨酰化可抑制凋亡。我们发现了ARS的非规范功能，并揭示了系统和功能性的氨基酸传感和信号转导网络。