ArticleProceedings of the National Academy of Sciences of the United States of America2013
eIF4E3 acts as a tumor suppressor by utilizing an atypical mode of methyl-7-guanosine cap recognition.
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 71 papers.
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Who cites it
71 citing papers in PubMed, 129 citations in OpenAlex.
- Escorting mRNAs - the multifunctional and divergent roles of cap-chaperones in post-transcriptional gene expression.Journal of cell science · 2026Review
- Proteolytic dissection of eIF4G reveals the closed-loop mRNP as an architecture for translation repression.bioRxiv : the preprint server for biology · 2026Article
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- m7G RNA methylation in cancer: Effect, mechanism and clinical application.Clinical and translational medicine · 2025Review
- RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.Journal of advanced research · 2025Article
- A Computational Recognition Analysis of Promising Prognostic Biomarkers in Breast, Colon and Lung Cancer Patients.International journal of molecular sciences · 2025Article
- The role of m5C, m1A and m7G modifications in tumors of urinary system.Frontiers in cell and developmental biology · 2025Review
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- eIF4E orchestrates mRNA processing, RNA export and translation to modify specific protein production.Nucleus (Austin, Tex.) · 2024Review
- Non-canonical mRNA translation initiation in cell stress and cancer.NAR cancer · 2024Review
- Dual role of GRHL3 in bladder carcinogenesis depending on histological subtypes.Molecular oncology · 2024Article
- Advances in prognostic models for osteosarcoma risk.Heliyon · 2024Review
- Identification and validation of NJournal of cellular and molecular medicine · 2024Article
- M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets.International journal of biological sciences · 2024Review
- eIF4E1b is a non-canonical eIF4E protecting maternal dormant mRNAs.EMBO reports · 2024Article
- A methylation-related signature for predicting prognosis and sensitivity to first-line therapies in gastric cancer.Journal of gastrointestinal oncology · 2023Article
- Analysis of m7G-Related signatures in the tumour immune microenvironment and identification of clinical prognostic regulators in breast cancer.BMC cancer · 2023Article
- Comprehensive multi-omics analysis reveals m7G-related signature for evaluating prognosis and immunotherapy efficacy in osteosarcoma.Journal of bone oncology · 2023Article
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11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Recognition of the methyl-7-guanosine (m(7)G) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E-cap recognition is mediated via complementary charge interactions of the positively charged m(7)G cap between the negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the m(7)G cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3-cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant.
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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.