Isoleucyl-tRNA synthetase 2 (IARS2) is a mitochondrial isoleucine-tRNA synthetase of the class I aminoacyl-tRNA synthetase family, and its role in cervical cancer remains poorly defined. Here, we report that IARS2 promotes cervical cancer cell proliferation and survival through regulation of the Rag GTPases and mTORC1. Elevated IARS2 expression was associated with poorer overall survival in patients with cervical cancer. Silencing of IARS2 significantly reduced cell viability and induced apoptosis in cervical cancer cells. Mechanistically, IARS2 inhibited mTOR degradation and sustained activation of the mTOR–eIF4E axis, thereby supporting cell proliferation. The amino acid–binding pocket of IARS2 was essential for these regulatory effects. Moreover, immunoprecipitation assays revealed that IARS2 interacted with Rag GTPases, particularly RagB and RagD. Together, these findings suggest that IARS2 may function as an amino acid sensor within the Rag–mTORC1 complex and highlight IARS2 as a potential therapeutic target in cervical cancer.
Bi et al. (Mon,) studied this question.