ArticleThe Journal of experimental medicine2021
Loss of tRNA-modifying enzyme Elp3 activates a p53-dependent antitumor checkpoint in hematopoiesis.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells.Nature communications · 2026Article
- Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion.Histology and histopathology · 2026Article
- BRD4-associated chromatin remodelling signature links epigenetic regulation to immune landscape in ovarian cancer.Journal of ovarian research · 2026Article
- Advances in RNA modification in myocardial fibrosis (Review).International journal of molecular medicine · 2025Review
- Upregulation of ELP3 in acinar cells during acute pancreatitis is dispensable for homeostasis, inflammation, regeneration, and cancer initiation.Scientific reports · 2025Article
- Pan-cancer analysis identifies tRNA modification enzyme CTU2 as a novel tumor biomarker and its role in immune microenvironment.Frontiers in immunology · 2025Article
- Loss of Elp3 blocks intestinal tuft cell differentiation via an mTORC1-Atf4 axis.The EMBO journal · 2024Article
- ELP3 stabilizes c-Myc to promote tumorigenesis.Journal of molecular cell biology · 2024Article
- EPC1/2 regulate hematopoietic stem and progenitor cell proliferation by modulating H3 acetylation and DLST.iScience · 2024Article
- The impact of tRNA modifications on translation in cancer: identifying novel therapeutic avenues.NAR cancer · 2024Review
- RNA modifications in physiology and disease: towards clinical applications.Nature reviews. Genetics · 2024Review
- The conserved wobble uridine tRNA thiolase Ctu1 is required for angiogenesis and embryonic development.PloS one · 2024Article
- RNA modification in cardiovascular disease: implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis.Frontiers in molecular biosciences · 2023Review
- Dysfunctional tRNA reprogramming and codon-biased translation in cancer.Trends in molecular medicine · 2022Review
- Elp3-mediated codon-dependent translation promotes mTORC2 activation and regulates macrophage polarization.The EMBO journal · 2022Article
- Iron-sulfur clusters as inhibitors and catalysts of viral replication.Nature chemistry · 2022Review
- tRNA Function and Dysregulation in Cancer.Frontiers in cell and developmental biology · 2022Review
- The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
The hematopoietic system is highly sensitive to perturbations in the translational machinery, of which an emerging level of regulation lies in the epitranscriptomic modification of transfer RNAs (tRNAs). Here, we interrogate the role of tRNA anticodon modifications in hematopoiesis by using mouse models of conditional inactivation of Elp3, the catalytic subunit of Elongator that modifies wobble uridine in specific tRNAs. Loss of Elp3 causes bone marrow failure by inducing death in committing progenitors and compromises the grafting activity of hematopoietic stem cells. Mechanistically, Elp3 deficiency activates a p53-dependent checkpoint in what resembles a misguided amino acid deprivation response that is accompanied by Atf4 overactivation and increased protein synthesis. While deletion of p53 rescues hematopoiesis, loss of Elp3 prompts the development of p53-mutated leukemia/lymphoma, and inactivation of p53 and Elongator cooperatively promotes tumorigenesis. Specific tRNA-modifying enzymes thus condition differentiation and antitumor fate decisions in hematopoietic stem cells and progenitors.
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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 OpenQuestion graph.