ArticleProceedings of the National Academy of Sciences of the United States of America2013
Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 167 citations in OpenAlex.
- Sexual dimorphism of autism-like phenotypes in microglial eIF4E overexpression mice.bioRxiv : the preprint server for biology · 2026Article
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Dynamic redistribution of eIF4F controls cap-dependent translation initiation.bioRxiv : the preprint server for biology · 2026Article
- Remodeling of mRNA by eIF4F in human translation initiation.bioRxiv : the preprint server for biology · 2026Article
- A ribosomal kinetic checkpoint governs selective mRNA recruitment.bioRxiv : the preprint server for biology · 2026Article
- Nanometer-scale RNA protein clusters (RPCs) Foster Helicase Activity of DEAD-box eIF4A.bioRxiv : the preprint server for biology · 2026Article
- Purification and characterization of recombinant human translation initiation factor eIF3.Protein science : a publication of the Protein Society · 2026Article
- WDR4 drives tumour-associated macrophage reprogramming and tumour progression via selective translation and membrane cholesterol efflux.Nature cell biology · 2025Article
- Beyond the niche - unlocking the full potential of synthetic riboswitches.Nature communications · 2025Review
- eIF1 and eIF5 dynamically control translation start site fidelity.Nature structural & molecular biology · 2025Article
- 40S ribosomal subunits scan mRNA for the start codon by one-dimensional diffusion.RNA (New York, N.Y.) · 2025Article
- Dynamics and Regulation of mRNA Cap Recognition by Human eIF4F.bioRxiv : the preprint server for biology · 2025Article
- Conserved long-range interactions are required for stable folding of orthoflaviviral genomic RNA.Nucleic acids research · 2025Article
- The mechanism of mRNA cap recognition.Nature · 2025Article
- Translation regulation in response to stress.The FEBS journal · 2024Review
- Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function.Nature communications · 2024Article
- Review
- Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit.Nature communications · 2024Article
- The molecular basis of translation initiation and its regulation in eukaryotes.Nature reviews. Molecular cell biology · 2024Review
- The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A.Nature structural & molecular biology · 2024Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Elevated eukaryotic initiation factor 4E (eIF4E) levels frequently occur in a variety of human cancers. Overexpression of eIF4E promotes cellular transformation by selectively increasing the translation of proliferative and prosurvival mRNAs. These mRNAs possess highly structured 5'-UTRs that impede ribosome recruitment and scanning, yet the mechanism for how eIF4E abundance elevates their translation is not easily explained by its cap-binding activity. Here, we show that eIF4E possesses an unexpected second function in translation initiation by strongly stimulating eukaryotic initiation factor 4A (eIF4A) helicase activity. Importantly, we demonstrate that this activity promotes mRNA restructuring in a manner that is independent of its cap-binding function. To explain these findings, we show that the eIF4E-binding site in eukaryotic initiation factor 4G (eIF4G) functions as an autoinhibitory domain to modulate its ability to stimulate eIF4A helicase activity. Binding of eIF4E counteracts this autoinhibition, enabling eIF4G to stimulate eIF4A helicase activity. Finally, we have successfully separated the two functions of eIF4E to show that its helicase promoting activity increases the rate of translation by a mechanism that is distinct from its cap-binding function. Based on our results, we propose that maintaining a connection between eIF4E and eIF4G throughout scanning provides a plausible mechanism to explain how eIF4E abundance selectively stimulates the translation of highly structured proliferation and tumor-promoting mRNAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.