Isoleucyl-tRNA synthetase interactome

ABSTRACT: Aminoacyl-tRNA synthetases are key enzymes in protein synthesis, as they catalyze the attachment of amino acids to their designated, cognate tRNAs. As such, mutations in aminoacyl-tRNA synthetases are associated with severe diseases, such as neurodevelopmental disorders. Many of these mutations fall into the catalytic active site or tRNA binding domains, however, others can affect protein complex formation. Here, we investigate a disease-causing mutation in the UNE-L domain of Isoleucyl-tRNA synthetase (IARS1, IleRS), which interferes with multisynthetase complex formation. Interestingly, levels of the resulting protein are severely reduced in comparison to wildtype IleRS. While bulk protein synthesis and cell proliferation were not affected, the integrated stress response signaling pathway was altered. This change was exacerbated in low glucose medium, suggesting that mutant cells could respond differently to cellular stress. Our study hints at a new underlying disease mechanism, where catalytic activity might not be affected but instead complex formation and protein stability.  

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Haissi Cui  

LAB HEAD: Haissi Cui

PROVIDER: PXD067475 | Pride | 2026-03-02

REPOSITORIES: Pride