ArticleMolecular cell2019
The Translation Inhibitor Rocaglamide Targets a Bimolecular Cavity between eIF4A and Polypurine RNA.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 199 citations in OpenAlex.
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly.ACS central science · 2026Article
- Rocaglates and pateamines target the DEAD-box RNA helicase eIF4A from Schistosoma mansoni and demonstrate anti-schistosomal activity in vitro.Scientific reports · 2026Article
- Selective mRNA translation determines adaptative mutability of melanoma cells to anti-BRAF/MEK combination therapy.EMBO molecular medicine · 2026Article
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- Position-dependent codon occurrence is associated with patterns of translational efficiency and ribosomal occupancy in the human transcriptome.PLoS computational biology · 2026Article
- Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5.European journal of medicinal chemistry · 2026Article
- A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026Article
- Applications of Integrated Molecular Dynamics and Fragment Molecular Orbital (MD+FMO) Calculations in Drug Discovery and Structural Biology.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The RNA helicase eIF4A as a novel target in insect cells to combat arboviral infections.PloS one · 2026Article
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- Target agnostic cellular screening in the era of chemically induced proximity.RSC medicinal chemistry · 2025Review
- Blocking NRF2 Translation by Inhibition of Cap-Dependent Initiation Sensitizes Lymphoma Cells to Ferroptosis and CAR T-cell Immunotherapy.Cancer research · 2025Article
- Connecting chemical structure to single cell signaling profiles.Communications biology · 2025Article
- Targeting eIF4A with RNA Aptamers Enhances Salt Stress Tolerance in Rice Through Modulation of Translation Initiation.Rice (New York, N.Y.) · 2025Article
- Ribosome association inhibits stress-induced gene mRNA localization to stress granules.Genes & development · 2025Article
- Targeting translation initiation yields fast-killing therapeutics against the zoonotic parasite Cryptosporidium parvum.PLoS pathogens · 2025Article
- Advances in ribosome profiling technologies.Biochemical Society transactions · 2025Review
- Small-molecule RNA therapeutics to target prostate cancer.Cancer cell · 2025Article
- A structural element within the 5'UTR of β-catenin mRNA modulates its translation under hypoxia.Nucleic acids research · 2025Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 2 countries.
Funding
Abstract
A class of translation inhibitors, exemplified by the natural product rocaglamide A (RocA), isolated from Aglaia genus plants, exhibits antitumor activity by clamping eukaryotic translation initiation factor 4A (eIF4A) onto polypurine sequences in mRNAs. This unusual inhibitory mechanism raises the question of how the drug imposes sequence selectivity onto a general translation factor. Here, we determined the crystal structure of the human eIF4A1⋅ATP analog⋅RocA⋅polypurine RNA complex. RocA targets the "bi-molecular cavity" formed characteristically by eIF4A1 and a sharply bent pair of consecutive purines in the RNA. Natural amino acid substitutions found in Aglaia eIF4As changed the cavity shape, leading to RocA resistance. This study provides an example of an RNA-sequence-selective interfacial inhibitor fitting into the space shaped cooperatively by protein and RNA with specific sequences.
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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.