ArticleProceedings of the National Academy of Sciences of the United States of America2022
Inhibitors of eIF4G1-eIF1 uncover its regulatory role of ER/UPR stress-response genes independent of eIF2α-phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Elongationless start-stop elements are stress-resilient translation gates that are more repressive than uTranslons.Nucleic acids research · 2026Article
- Structural and molecular basis of specialized translation mediated by the ribosome mRNA-binding channel.Nature communications · 2026Article
- Nuclear import of malaria RNA rewires splicing in host immune cells.Cell reports · 2026Article
- VPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells.Cellular & molecular biology letters · 2026Article
- The organization principles of P. falciparum translation initiation features and their potential as drug targets.Nucleic acids research · 2025Article
- Inhibitors of eIF1A-ribosome interaction unveil uORF-dependent regulation of translation initiation and antitumor and antiviral effects.The EMBO journal · 2025Article
- Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.International journal of molecular sciences · 2024Review
- Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.bioRxiv : the preprint server for biology · 2024Article
- Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury.BMC cardiovascular disorders · 2024Article
- Comparing the Blood Response to Hyperbaric Oxygen with High-Intensity Interval Training-A Crossover Study in Healthy Volunteers.Antioxidants (Basel, Switzerland) · 2023Article
- Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding.Nucleic acids research · 2023Article
- Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story.RNA (New York, N.Y.) · 2023Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During translation initiation, eIF4G1 dynamically interacts with eIF4E and eIF1. While the role of eIF4E-eIF4G1 is well established, the regulatory functions of eIF4G1-eIF1 are poorly understood. Here, we report the identification of the eIF4G1-eIF1 inhibitors i14G1-10 and i14G1-12. i14G1s directly bind eIF4G1 and inhibit translation in vitro and in the cell, and their effects on translation are dependent on eIF4G1 levels. Translatome analyses revealed that i14G1s mimic eIF1 and eIF4G1 perturbations on the stringency of start codon selection and the opposing roles of eIF1-eIF4G1 in scanning-dependent and scanning-independent short 5' untranslated region (UTR) translation. Remarkably, i14G1s activate ER/unfolded protein response (UPR) stress-response genes via enhanced ribosome loading, elevated 5'UTR translation at near-cognate AUGs, and unexpected concomitant up-regulation of coding-region translation. These effects are, at least in part, independent of eIF2α-phosphorylation. Interestingly, eIF4G1-eIF1 interaction itself is negatively regulated by ER stress and mTOR inhibition. Thus, i14G1s uncover an unknown mechanism of ER/UPR translational stress response and are valuable research tools and potential drugs against diseases exhibiting dysregulated translation.
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