ArticleScience advances2023
Arginine limitation drives a directed codon-dependent DNA sequence evolution response in colorectal cancer cells.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 30 citations in OpenAlex.
- FGFR4-associated APOBEC3 mutagenesis characterizes HER2-enriched subtype of human breast cancer.British journal of cancer · 2026Article
- Article
- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- Arginine Deprivation of ASS1-Deficient Cancers Drives Mistranslation and Shared Neoepitope Production.Cancer research · 2026Article
- Clinically observed RASA1 missense mutants exhibit diverse RasGAP protein behaviors in vitro.The Journal of biological chemistry · 2026Article
- Convergent Evolution in Tumor Genomes Targets Functional Domains.bioRxiv : the preprint server for biology · 2026Article
- Hypoalbuminemia induces immunosuppression through disorder in macrophages and drives resistance to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2026Article
- Ribosome-associated quality control of aberrant protein production during amino acid limitation.bioRxiv : the preprint server for biology · 2026Article
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- Molecular mechanisms and therapies for tumor inhibition through the arginine metabolism pathway.Frontiers in oncology · 2026Review
- Exploiting nanopore sequencing advances for tRNA sequencing of human cancer models.NAR cancer · 2025Article
- Methylarginine Levels in Chronic Inflammatory Skin Diseases-The Role of L-Arginine/Nitric Oxide Pathway.Journal of clinical medicine · 2025Review
- Endothelial Arginine Metabolism in Angiogenesis: Mechanistic Insights from Tissue Repair to Tumor Progression.Metabolites · 2025Review
- Clinically observedbioRxiv : the preprint server for biology · 2025Article
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Adaptation to Arginine Deprivation Leads to a More Aggressive, Therapy-Resistant Phenotype in HNSCC Cells.Biomolecules · 2025Article
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Dengue virus preferentially uses human and mosquito non-optimal codons.Molecular systems biology · 2024Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Utilization of specific codons varies between organisms. Cancer represents a model for understanding DNA sequence evolution and could reveal causal factors underlying codon evolution. We found that across human cancer, arginine codons are frequently mutated to other codons. Moreover, arginine limitation-a feature of tumor microenvironments-is sufficient to induce arginine codon-switching mutations in human colon cancer cells. Such DNA codon switching events encode mutant proteins with arginine residue substitutions. Mechanistically, arginine limitation caused rapid reduction of arginine transfer RNAs and the stalling of ribosomes over arginine codons. Such selective pressure against arginine codon translation induced an adaptive proteomic shift toward low-arginine codon-containing genes, including specific amino acid transporters, and caused mutational evolution away from arginine codons-reducing translational bottlenecks that occurred during arginine starvation. Thus, environmental availability of a specific amino acid can influence DNA sequence evolution away from its cognate codons and generate altered proteins.
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Registered trials
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.