eIF4E integrates into stress response

In this issue, Diamond et al. 1 Diamond P.D. McGlincy N.J. Ingolia N.T. Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression. Mol. Cell. 2024; 84: 2119-2134.e5 Google Scholar and Kim et al. 2 Kim K.Q. Nanjaraj Urs A.N. Lasehinde V. Greenlaw A.C. Hudson B.H. Zaher H.S. eIF4F complex dynamics are important for the activation of the integrated stress response. Mol. Cell. 2024; 84: 2135-2151.e7 Google Scholar report that depletion of eIF4E leads to translational upregulation of GCN4, a key player in the integrated stress response, in an eIF2α phosphorylation-independent manner, suggesting a new mode of translational adaptation. In this issue, Diamond et al. 1 Diamond P.D. McGlincy N.J. Ingolia N.T. Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression. Mol. Cell. 2024; 84: 2119-2134.e5 Google Scholar and Kim et al. 2 Kim K.Q. Nanjaraj Urs A.N. Lasehinde V. Greenlaw A.C. Hudson B.H. Zaher H.S. eIF4F complex dynamics are important for the activation of the integrated stress response. Mol. Cell. 2024; 84: 2135-2151.e7 Google Scholar report that depletion of eIF4E leads to translational upregulation of GCN4, a key player in the integrated stress response, in an eIF2α phosphorylation-independent manner, suggesting a new mode of translational adaptation. eIF4F complex dynamics are important for the activation of the integrated stress responseKim et al.Molecular CellJune 06, 2024In BriefClassically, the ISR is activated through the phosphorylation of eIF2α. Here, Kim et al. show that when eIF4E levels are depleted, the pathway is induced via a novel mechanism in which the altered ratio of heterotrimeric eIF4F complex components appears to change scanning dynamics, resulting in de-repression of GCN4 translation. Full-Text PDF Open AccessDepletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expressionDiamond et al.Molecular CellJune 06, 2024In BriefThe cap-binding protein eIF4E protects mRNAs from degradation and promotes their translation. Although eIF4E is essential, Diamond et al. show that yeast survive and adapt after near total eIF4E depletion. Acute depletion of cap-binding protein reduces expression of short, highly expressed mRNAs at multiple levels and dysregulates amino acid metabolic genes. Full-Text PDF