ArticleNucleic acids research2018
eIF4A alleviates the translational repression mediated by classical secondary structures more than by G-quadruplexes.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
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- An update on cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer.Future oncology (London, England) · 2025Review
- Eukaryotic initiation factor 4B is a multi-functional RNA binding protein that regulates histone mRNAs.Nucleic acids research · 2024Article
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- The shaping of mRNA translation plasticity by RNA G-quadruplexes in cancer progression and therapy resistance.NAR cancer · 2024Review
- The MYCN 5' UTR as a therapeutic target in neuroblastoma.Cell reports · 2024Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- Role of eIF4A1 in triple-negative breast cancer stem-like cell-mediated drug resistance.Cancer reports (Hoboken, N.J.) · 2022Article
- 5' Untranslated mRNA Regions Allow Bypass of Host Cell Translation Inhibition by Legionella pneumophila.Infection and immunity · 2022Article
- Action and function of helicases on RNA G-quadruplexes.Methods (San Diego, Calif.) · 2022Review
- m6A and YTHDF proteins contribute to the localization of select neuronal mRNAs.Nucleic acids research · 2022Article
- The different activities of RNA G-quadruplex structures are controlled by flanking sequences.Life science alliance · 2022Article
- The Role of Breast Cancer Stem Cells in Chemoresistance and Metastasis in Triple-Negative Breast Cancer.Cancers · 2021Review
- Transcription, translation, and DNA repair: new insights from emerging noncanonical substrates of RNA helicases.Biological chemistry · 2021Review
- Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back.Nucleic acids research · 2020Article
- RNA G-quadruplex structures exist and function in vivo in plants.Genome biology · 2020Article
- Article
- General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation.International journal of molecular sciences · 2020Review
- Translational profiling of macrophages infected with Leishmania donovani identifies mTOR- and eIF4A-sensitive immune-related transcripts.PLoS pathogens · 2020Article
- KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation.PloS one · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Increased activity of the mRNA helicase eIF4A drives cellular malignancy by reprogramming cellular translation, and eIF4A activity is the direct or indirect target of many emerging cancer therapeutics. The enriched presence of (GGC)4 motifs, which have the potential to fold into two-layered G-quadruplexes, within the 5'UTRs of eIF4A-dependent mRNAs suggests that eIF4A is required for the unwinding of these structures within these eIF4A-controlled mRNAs. However, the existence of folded G-quadruplexes within cells remains controversial, and G-quadruplex folding is in direct competition with classical Watson-Crick based secondary structures. Using a combination of reverse transcription stalling assays and 7-deazaguanine incorporation experiments we find that (GGC)4 motifs preferentially form classical secondary structures rather than G-quadruplexes in full-length mRNAs. Furthermore, using translation assays with the eIF4A inhibitor hippuristanol, both in vitro and in cells, we find that eIF4A activity alleviates translational repression of mRNAs with 5'UTR classical secondary structures significantly more than those with folded G-quadruplexes. This was particularly evident in experiments using a G-quadruplex stabilizing ligand, where shifting the structural equilibrium in favour of G-quadruplex formation diminishes eIF4A-dependency. This suggests that enrichment of (GGC)4 motifs in the 5'UTRs of eIF4A-dependent mRNAs is due to the formation of stable hairpin structures rather than G-quadruplexes.
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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.