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

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

Yusuke Tsukamoto  1   2 , Yumi Nakamura  1   2 , Makoto Hirata  3 , Daisuke Okuzaki  4 , Ryuichi Sakate  3 , Tomonori Kimura  1   2   3   5
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Free article

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

Yusuke Tsukamoto et al. FEBS Lett. 2023 Jun.
Free article

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 tRNAGln (CUG) reflects cellular glutamine level. When uncharged tRNAGln (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 tRNAGln (CUG) charging levels. Thus, tRNA charging is sensitive to intracellular nutrient status and is an important initiator of intracellular signaling.

Keywords: GCN2; charging; glutamine; nutrition; tRNA; ubiquitin.

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