eIF4F complex dynamics are important for the activation of the integrated stress response

Published: 16 April 2024| Version 1 | DOI: 10.17632/gg5zwy34bc.1
Kyusik Kim,
, Victor Lasehinde, Alison Greenlaw, Benjamin Hudson, Hani Zaher


In response to stress, eukaryotes activate the integrated stress response (ISR) via phosphorylation of eIF2α to promote the translation of pro-survival effector genes, such as GCN4 in yeast. Complementing the ISR is the Target of Rapamycin (TOR) pathway, which regulates eIF4E function. Here we probe translational control in the absence of eIF4E in Saccharomyces cerevisiae. Intriguingly, we find that loss of eIF4E leads to de-repression of GCN4 translation. In addition, we find that de-repression of GCN4 translation is neither accompanied by eIF2α phosphorylation nor reduction in initiator ternary complex. Our data suggest that when eIF4E levels are depleted, GCN4 translation is de-repressed via a unique mechanism that may involve faster scanning by the small ribosome subunit due to increased local concentration of eIF4A. Overall, our findings suggest that relative levels of eIF4F components are key to ribosome dynamics and may play important roles in translational control of gene expression.



Washington University in St. Louis


Protein Synthesis, RNA, Ribosome, Cellular Stress Response, Initiation Complex, Control of Translation, Yeast Model


National Institutes of Health

R01GM112641 and R01GM141474