美国斯克里普斯研究所Paul Schimmel等研究人员合作发现，精氨酸-tRNA合成酶通过SRRM2将炎症代谢与RNA剪接和核运输联系起来。相关论文于2023年4月14日在线发表在《自然—细胞生物学》杂志上。

研究人员发现，在炎症期间，精氨酸的耗尽降低了核定位的精氨酰-tRNA合成酶（ArgRS）的水平。令人惊讶的是，研究人员发现核ArgRS与丝氨酸/精氨酸重复基质蛋白2（SRRM2）相互作用并共同定位，SRRM2是一种剪接体和核斑点蛋白，核ArgRS水平的下降与SRRM2的凝聚状核运输和某些基因的剪接位点使用变化有关。这些剪接位点使用的变化累积在不同的蛋白质亚型的合成中，并改变了细胞的代谢和肽对免疫细胞的表达。这些研究结果揭示了一种机制，即一个与炎症期间代谢控制的关键氨基酸相关氨基酸酰基-tRNA合成酶可以调节剪接机器。

据介绍，细胞通过感知代谢物水平的变化对诸如炎症等扰动作出反应。特别突出的是精氨酸，它与炎症反应有已知的联系。氨基酸酰基-tRNA合成酶是催化蛋白质合成的第一步的酶，也可以介导细胞信号。

附：英文原文

Title: Arg-tRNA synthetase links inflammatory metabolism to RNA splicing and nuclear trafficking via SRRM2

Author: Cui, Haissi, Diedrich, Jolene K., Wu, Douglas C., Lim, Justin J., Nottingham, Ryan M., Moresco, James J., Yates, John R., Blencowe, Benjamin J., Lambowitz, Alan M., Schimmel, Paul

Issue&Volume: 2023-04-14

Abstract: Cells respond to perturbations such as inflammation by sensing changes in metabolite levels. Especially prominent is arginine, which has known connections to the inflammatory response. Aminoacyl-tRNA synthetases, enzymes that catalyse the first step of protein synthesis, can also mediate cell signalling. Here we show that depletion of arginine during inflammation decreased levels of nuclear-localized arginyl-tRNA synthetase (ArgRS). Surprisingly, we found that nuclear ArgRS interacts and co-localizes with serine/arginine repetitive matrix protein 2 (SRRM2), a spliceosomal and nuclear speckle protein, and that decreased levels of nuclear ArgRS correlated with changes in condensate-like nuclear trafficking of SRRM2 and splice-site usage in certain genes. These splice-site usage changes cumulated in the synthesis of different protein isoforms that altered cellular metabolism and peptide presentation to immune cells. Our findings uncover a mechanism whereby an aminoacyl-tRNA synthetase cognate to a key amino acid that is metabolically controlled during inflammation modulates the splicing machinery.

DOI: 10.1038/s41556-023-01118-8

Source: https://www.nature.com/articles/s41556-023-01118-8