ArticleMolecular cell2024
Depletion of cap-binding protein eIF4E dysregulates amino acid metabolic gene expression.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Heat stress promotes pre-tRNA capping to modulate cap-dependent translation in Saccharomyces cerevisiae.Nature communications · 2026Article
- Genes for 5'mRNA cap binding proteins, eif4ea and eif4eb, have alternative roles during heart regeneration.Developmental biology · 2026Article
- NNature · 2026Article
- Insights into the role of collided ribosomes during the activation of the integrated stress response.Biochemical Society transactions · 2025Review
- Precise measurement of molecular phenotypes with barcode-based CRISPRi systems.Genome biology · 2025Article
- Mapping the Genetic Architecture of the Adaptive Integrated Stress Response inbioRxiv : the preprint server for biology · 2024Article
- CRISPRi with barcoded expression reporters dissects regulatory networks in human cells.bioRxiv : the preprint server for biology · 2024Article
- eIF4F complex dynamics are important for the activation of the integrated stress response.Molecular cell · 2024Article
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Abstract
Protein synthesis is metabolically costly and must be tightly coordinated with changing cellular needs and nutrient availability. The cap-binding protein eIF4E makes the earliest contact between mRNAs and the translation machinery, offering a key regulatory nexus. We acutely depleted this essential protein and found surprisingly modest effects on cell growth and recovery of protein synthesis. Paradoxically, impaired protein biosynthesis upregulated genes involved in the catabolism of aromatic amino acids simultaneously with the induction of the amino acid biosynthetic regulon driven by the integrated stress response factor GCN4. We further identified the translational control of Pho85 cyclin 5 (PCL5), a negative regulator of Gcn4, that provides a consistent protein-to-mRNA ratio under varied translation environments. This regulation depended in part on a uniquely long poly(A) tract in the PCL5 5' UTR and poly(A) binding protein. Collectively, these results highlight how eIF4E connects protein synthesis to metabolic gene regulation, uncovering mechanisms controlling translation during environmental challenges.
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