ArticleCellular and molecular life sciences : CMLS2022
Upstream open reading frames regulate translation of cancer-associated transcripts and encode HLA-presented immunogenic tumor antigens.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- HLA class I-naturally presented synovial tissue peptides are recognized by CD8+ T lymphocytes from rheumatoid arthritis patients.Frontiers in immunology · 2026Article
- Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.RNA biology · 2025Review
- CTG-Initiated Cryptic Peptide Translation Up- and Downstream of a Canonical ATG Start Codon Is Enhanced by TLR Stimulation and Induces Tumor Regression in Mice.Cancer immunology research · 2025Article
- CircRNAs in Colorectal Cancer: Unveiling Their Roles and Exploring Therapeutic Potential.Biochemical genetics · 2025Review
- Unveiling conserved HIV-1 open reading frames encoding T cell antigens using ribosome profiling.Nature communications · 2025Article
- Non-canonical translation in cancer: significance and therapeutic potential of non-canonical ORFs, mCell death discovery · 2024Review
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides.Nature communications · 2024Article
- An epitope encoded by uORF ofMolecular therapy oncolytics · 2023Article
- Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.Blood cancer discovery · 2023Article
- DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts.Nature communications · 2023Article
- Review
- Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through Proteogenomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Employing non-targeted interactomics approach and subcellular fractionation to increase our understanding of the ghost proteome.iScience · 2023Article
- The new uORFdb: integrating literature, sequence, and variation data in a central hub for uORF research.Nucleic acids research · 2023Article
- The Emerging Role of uORF-Encoded uPeptides and HLA uLigands in Cellular and Tumor Biology.Cancers · 2022Review
- Development of a novel hypoxia-immune-related LncRNA risk signature for predicting the prognosis and immunotherapy response of colorectal cancer.Frontiers in immunology · 2022Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundUpstream open reading frames (uORFs) represent translational control elements within eukaryotic transcript leader sequences. Recent data showed that uORFs can encode for biologically active proteins and human leukocyte antigen (HLA)-presented peptides in malignant and benign cells suggesting their potential role in cancer cell development and survival. However, the role of uORFs in translational regulation of cancer-associated transcripts as well as in cancer immune surveillance is still incompletely understood.
methodsWe examined the translational regulatory effect of 29 uORFs in 13 cancer-associated genes by dual-luciferase assays. Cellular expression and localization of uORF-encoded peptides (uPeptides) were investigated by immunoblotting and immunofluorescence-based microscopy. Furthermore, we utilized mass spectrometry-based immunopeptidome analyses in an extensive dataset of primary malignant and benign tissue samples for the identification of naturally presented uORF-derived HLA-presented peptides screening for more than 2000 uORFs.
resultsWe provide experimental evidence for similarly effective translational regulation of cancer-associated transcripts through uORFs initiated by either canonical AUG codons or by alternative translation initiation sites (aTISs). We further demonstrate frequent cellular expression and reveal occasional specific cellular localization of uORF-derived peptides, suggesting uPeptide-specific biological implications. Immunopeptidome analyses delineated a set of 125 naturally presented uORF-derived HLA-presented peptides. Comparative immunopeptidome profiling of malignant and benign tissue-derived immunopeptidomes identified several tumor-associated uORF-derived HLA ligands capable to induce multifunctional T cell responses.
conclusionOur data provide direct evidence for the frequent expression of uPeptides in benign and malignant human tissues, suggesting a potentially widespread function of uPeptides in cancer biology. These findings may inspire novel approaches in direct molecular as well as immunotherapeutic targeting of cancer-associated uORFs and uPeptides.
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