ArticlePloS one2024
JUN mRNA translation regulation is mediated by multiple 5' UTR and start codon features.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 7 citations in OpenAlex.
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- Identification of Cathepsin H and Metabolic Traits as Potential Biomarkers for Lung Cancer by Mendelian Randomization and Single-Cell Transcriptomics.Advanced genetics (Hoboken, N.J.) · 2025Article
- Distinct non-canonical translation initiation modes arise for specific host and viral mRNAs during poxvirus-induced shutoff.Nature microbiology · 2025Article
- Decoding post-transcriptional regulatory networks by RNA-linked CRISPR screening in human cells.Nature methods · 2025Article
- The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.Developmental cell · 2025Article
- Anti-tumor effects of the eIF4A inhibitor didesmethylrocaglamide and its derivatives in human and canine osteosarcomas.Scientific reports · 2024Article
- A dynamic compositional equilibrium governs mRNA recognition by eIF3.bioRxiv : the preprint server for biology · 2024Article
- Decoding RNA Metabolism by RNA-linked CRISPR Screening in Human Cells.bioRxiv : the preprint server for biology · 2024Article
- Anti-tumor Effects of the eIF4A Inhibitor Didesmethylrocaglamide and Its Derivatives in Human and Canine Osteosarcomas.Research square · 2024Article
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4 authors at 2 institutions in 1 country.
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Abstract
Regulation of mRNA translation by eukaryotic initiation factors (eIFs) is crucial for cell survival. In humans, eIF3 stimulates translation of the JUN mRNA which encodes the transcription factor JUN, an oncogenic transcription factor involved in cell cycle progression, apoptosis, and cell proliferation. Previous studies revealed that eIF3 activates translation of the JUN mRNA by interacting with a stem loop in the 5' untranslated region (5' UTR) and with the 5' -7-methylguanosine cap structure. In addition to its interaction site with eIF3, the JUN 5' UTR is nearly one kilobase in length, and has a high degree of secondary structure, high GC content, and an upstream start codon (uAUG). This motivated us to explore the complexity of JUN mRNA translation regulation in human cells. Here we find that JUN translation is regulated in a sequence and structure-dependent manner in regions adjacent to the eIF3-interacting site in the JUN 5' UTR. Furthermore, we identify contributions of an additional initiation factor, eIF4A, in JUN regulation. We show that enhancing the interaction of eIF4A with JUN by using the compound Rocaglamide A (RocA) represses JUN translation. We also find that both the upstream AUG (uAUG) and the main AUG (mAUG) contribute to JUN translation and that they are conserved throughout vertebrates. Our results reveal additional layers of regulation for JUN translation and show the potential of JUN as a model transcript for understanding multiple interacting modes of translation regulation.
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