ArticleGenome biology2019
mRNA structural elements immediately upstream of the start codon dictate dependence upon eIF4A helicase activity.
Article in Genome biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Curcumin inhibits chondrocyte apoptosis and inflammation in osteoarthritis via the miR-338-3p/EIF4A1 signaling axis.Hereditas · 2026Article
- TDP-43 binds to RNA G-quadruplex structure and regulates mRNA stability and translation.Nucleic acids research · 2025Article
- A structural element within the 5'UTR of β-catenin mRNA modulates its translation under hypoxia.Nucleic acids research · 2025Article
- Comparative analysis of translatomics and transcriptomics in the longissimus dorsi muscle of Luchuan and Duroc pigs.PloS one · 2025Article
- DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via mNature communications · 2024Article
- Eukaryotic initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs.Nucleic acids research · 2024Article
- eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition.Nature structural & molecular biology · 2024Article
- Identification of RNA structures and their roles in RNA functions.Nature reviews. Molecular cell biology · 2024Review
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- The MYCN 5' UTR as a therapeutic target in neuroblastoma.Cell reports · 2024Article
- In vivo structure probing of RNA inRNA (New York, N.Y.) · 2023Article
- Broad anti-pathogen potential of DEAD box RNA helicase eIF4A-targeting rocaglates.Scientific reports · 2023Article
- eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation.Nucleic acids research · 2023Article
- Article
- Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer.Frontiers in oncology · 2023Review
- Eukaryotic translation initiation factor 4A1 in the pathogenesis and treatment of cancers.Frontiers in molecular biosciences · 2023Review
- The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis.Molecular cell · 2022Article
- Action and function of helicases on RNA G-quadruplexes.Methods (San Diego, Calif.) · 2022Review
- Article
- An alternative UPF1 isoform drives conditional remodeling of nonsense-mediated mRNA decay.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe RNA helicase eIF4A1 is a key component of the translation initiation machinery and is required for the translation of many pro-oncogenic mRNAs. There is increasing interest in targeting eIF4A1 therapeutically in cancer, thus understanding how this protein leads to the selective re-programming of the translational landscape is critical. While it is known that eIF4A1-dependent mRNAs frequently have long GC-rich 5'UTRs, the details of how 5'UTR structure is resculptured by eIF4A1 to enhance the translation of specific mRNAs are unknown.
resultsUsing Structure-seq2 and polysome profiling, we assess global mRNA structure and translational efficiency in MCF7 cells, with and without eIF4A inhibition with hippuristanol. We find that eIF4A inhibition does not lead to global increases in 5'UTR structure, but rather it leads to 5'UTR remodeling, with localized gains and losses of structure. The degree of these localized structural changes is associated with 5'UTR length, meaning that eIF4A-dependent mRNAs have greater localized gains of structure due to their increased 5'UTR length. However, it is not solely increased localized structure that causes eIF4A-dependency but the position of the structured regions, as these structured elements are located predominantly at the 3' end of the 5'UTR.
conclusionsBy measuring changes in RNA structure following eIF4A inhibition, we show that eIF4A remodels local 5'UTR structures. The location of these structural elements ultimately determines the dependency on eIF4A, with increased structure just upstream of the CDS being the major limiting factor in translation, which is overcome by eIF4A activity.
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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.