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

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

Automated summary

Each tRNA can bind to an amino acid specific to a genetic codon. It is currently unclear what factors are associated with tRNA charging and how tRNA charging is maintained. Using the individual tRNA acylation PCR method, it was discovered that the charging ratio of tRNA(Gln)(CUG) reflects the cellular glutamine level. Activation of the kinase GCN2, a key stimulator of the integrated stress response, led to upregulation of ubiquitin C (UBC) expression, which in turn suppressed the further reduction in tRNA(Gln)(CUG) charging levels. Thus, tRNA charging is sensitive to intracellular nutrient status and plays a crucial role in intracellular signaling.