ArticleScientific reports2018
Loss-of-function uORF mutations in human malignancies.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 65 citations in OpenAlex.
- Elongationless start-stop elements are stress-resilient translation gates that are more repressive than uTranslons.Nucleic acids research · 2026Article
- A pathogen-induced translational shift enhances plant disease resistance without obvious fitness costs.aBIOTECH · 2026Article
- CRISPR-Cas9-mediated uATG introduction in the 5'UTR of the Uox gene for hyperuricemia mouse models: implications for gout and metabolic disorders.Science China. Life sciences · 2026Article
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- Novel start codon variant in the 5'UTR of LDLR associated with familial hypercholesterolaemia.European journal of human genetics : EJHG · 2026Article
- The birth, death, and evolutionary compensation of uORFs in Drosophila.Nucleic acids research · 2026Article
- Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.RNA biology · 2025Review
- Bioinformatics frameworks for single-cell long-read sequencing: unlocking isoform-level resolution.Briefings in bioinformatics · 2025Review
- The role of untranslated region variants in Mendelian disease: a review.European journal of human genetics : EJHG · 2025Review
- MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays.The EMBO journal · 2025Article
- A novel uORF regulates folliculin to promote cell growth and lysosomal biogenesis during cardiac stress.Scientific reports · 2025Article
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.Cell communication and signaling : CCS · 2024Review
- Article
- azyx-1 is a new gene that overlaps with zyxin and affects its translation in C. elegans, impacting muscular integrity and locomotion.PLoS biology · 2023Article
- Principles, mechanisms, and biological implications of translation termination-reinitiation.RNA (New York, N.Y.) · 2023Article
- Annotation of uORFs in the OMIM genes allows to reveal pathogenic variants in 5'UTRs.Nucleic acids research · 2023Article
- The Functional Meaning of 5'UTR in Protein-Coding Genes.International journal of molecular sciences · 2023Review
- The new uORFdb: integrating literature, sequence, and variation data in a central hub for uORF research.Nucleic acids research · 2023Article
- Re-evaluating the impact of alternative RNA splicing on proteomic diversity.Frontiers in genetics · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribosome profiling revealed widespread translational activity at upstream open reading frames (uORFs) and validated uORF-mediated translational control as a commonly repressive mechanism of gene expression. Translational activation of proto-oncogenes through loss-of-uORF mutations has been demonstrated, yet a systematic search for cancer-associated genetic alterations in uORFs is lacking. Here, we applied a PCR-based, multiplex identifier-tagged deep sequencing approach to screen 404 uORF translation initiation sites of 83 human tyrosine kinases and 49 other proto-oncogenes in 308 human malignancies. We identified loss-of-function uORF mutations in EPHB1 in two samples derived from breast and colon cancer, and in MAP2K6 in a sample of colon adenocarcinoma. Both mutations were associated with enhanced translation, suggesting that loss-of-uORF-mediated translational induction of the downstream main protein coding sequence may have contributed to carcinogenesis. Computational analysis of whole exome sequencing datasets of 464 colon adenocarcinomas subsequently revealed another 53 non-recurrent somatic mutations functionally deleting 22 uORF initiation and 31 uORF termination codons, respectively. These data provide evidence for somatic mutations affecting uORF initiation and termination codons in human cancer. The insufficient coverage of uORF regions in current whole exome sequencing datasets demands for future genome-wide analyses to ultimately define the contribution of uORF-mediated translational deregulation in oncogenesis.
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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 Socratic graph.