Title
Stress-induced perturbations in intracellular amino acids reprogram mRNA translation in osmoadaptation independently of the ISR
Document Type
Article
Publication Date
7-19-2022
Abstract
The integrated stress response (ISR) plays a pivotal role in adaptation of translation machinery to cellular stress. Here, we demonstrate an ISR-independent osmoadaptation mechanism involving reprogramming of translation via coordinated but independent actions of mTOR and plasma membrane amino acid transporter SNAT2. This biphasic response entails reduced global protein synthesis and mTOR signaling followed by translation of SNAT2. Induction of SNAT2 leads to accumulation of amino acids and reactivation of mTOR and global protein synthesis, paralleled by partial reversal of the early-phase, stress-induced translatome. We propose SNAT2 functions as a molecular switch between inhibition of protein synthesis and establishment of an osmoadaptive translation program involving the formation of cytoplasmic condensates of SNAT2-regulated RNA-binding proteins DDX3X and FUS. In summary, we define key roles of SNAT2 in osmotolerance.
Publication Source (Journal or Book title)
Cell reports
First Page
111092
Recommended Citation
Krokowski, D., Jobava, R., Szkop, K. J., Chen, C., Fu, X., Venus, S., Guan, B., & Wu, J. (2022). Stress-induced perturbations in intracellular amino acids reprogram mRNA translation in osmoadaptation independently of the ISR. Cell reports, 40 (3), 111092. https://doi.org/10.1016/j.celrep.2022.111092