ArticleProceedings of the National Academy of Sciences of the United States of America2020
Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 56 citations in OpenAlex.
- tRNA modifications in viral replication.The Journal of biological chemistry · 2026Review
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- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Essentiality and dynamic expression of the human tRNA pool during viral infection.Molecular systems biology · 2026Article
- Tissue-specific role of dTrmO in threonine decoding during Drosophila melanogaster development.Biological research · 2026Article
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Exploiting nanopore sequencing advances for tRNA sequencing of human cancer models.NAR cancer · 2025Article
- tRNA modifications: greasing the wheels of translation and beyond.RNA biology · 2025Review
- Chemically modified tRNA enhances the translation capacity of mRNA rich in cognate codons.Nature communications · 2025Article
- Connecting tRNA Charging and Decoding through the Axis of Nucleotide Modifications at Position 37.Journal of molecular biology · 2025Review
- MapID-based quantitative mapping of chemical modifications and expression of human transfer RNA.Cell chemical biology · 2025Article
- Translation dysregulation in cancer as a source for targetable antigens.Cancer cell · 2025Article
- Queuosine tRNA Modification: Connecting the Microbiome to the Translatome.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation.International journal of molecular sciences · 2025Article
- Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma-A Pilot Study.International journal of molecular sciences · 2024Article
- Cellular and clinical impact of protein phosphatase enzyme epigenetic silencing in multiple cancer tissues.Human genomics · 2024Article
- The impact of tRNA modifications on translation in cancer: identifying novel therapeutic avenues.NAR cancer · 2024Review
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- Translational response to mitochondrial stresses is orchestrated by tRNA modifications.bioRxiv : the preprint server for biology · 2024Article
- RNA modifications in physiology and disease: towards clinical applications.Nature reviews. Genetics · 2024Review
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14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNAs (mRNAs). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology.
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