GCN2 激酶介导的泛素 C 的上调在氨基酸饥饿下维持细胞内谷氨酰胺水平和 tRNA（CUG）的加载。

GCN2 kinase-mediated upregulation of ubiquitin C maintains intracellular glutamine level and tRNA (CUG) charging under amino acid starvation.

机构信息

Reverse Translational Research Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki, Japan.

KAGAMI Project, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Ibaraki, Japan.

出版信息

FEBS Lett. 2023 Jun;597(12):1638-1650. doi: 10.1002/1873-3468.14628. Epub 2023 May 2.

DOI:10.1002/1873-3468.14628

PMID:37079003

Abstract

Each tRNA is aminoacylated (charged) with a genetic codon-specific amino acid. It remains unclear what factors are associated with tRNA charging and how tRNA charging is maintained. By using the individual tRNA acylation PCR method, we found that the charging ratio of tRNA (CUG) reflects cellular glutamine level. When uncharged tRNA (CUG) increased under amino acid starvation, the kinase GCN2, which is a key stimulator of the integrated stress response, was activated. Activation of GCN2 led to the upregulation of ubiquitin C (UBC) expression. Upregulated UBC, in turn, suppressed the further reduction in tRNA (CUG) charging levels. Thus, tRNA charging is sensitive to intracellular nutrient status and is an important initiator of intracellular signaling.

摘要

每种 tRNA 都与特定的遗传密码子对应的氨基酸进行氨酰化（充电）。目前尚不清楚与 tRNA 充电相关的因素有哪些，以及如何维持 tRNA 充电。通过使用个体 tRNA 酰化 PCR 方法，我们发现 tRNA（CUG）的充电率反映了细胞中的谷氨酰胺水平。在氨基酸饥饿时，当未充电的 tRNA（CUG）增加时，作为整合应激反应关键刺激物的激酶 GCN2 被激活。GCN2 的激活导致泛素 C（UBC）表达上调。上调的 UBC 反过来又抑制了 tRNA（CUG）充电水平的进一步降低。因此，tRNA 充电对细胞内营养状况敏感，是细胞内信号的重要启动子。