ArticleThe EMBO journal2022
Elp3-mediated codon-dependent translation promotes mTORC2 activation and regulates macrophage polarization.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Histone and Histone Acetylation-Related Alterations of Gene Expression in Uninvolved Psoriatic Skin and Their Effects on Cell Proliferation, Differentiation, and Immune Responses.International journal of molecular sciences · 2023Pooled it
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- Transfer RNA Modifications in the Immune System Participate in Disease Pathogenesis.International journal of molecular sciences · 2026Review
- Identification of biomarkers associated with mitochondria and macrophage polarization in acute myocardial infarction: a bioinformatics analysis and validation study.Journal of cardiothoracic surgery · 2026Article
- MTFR2 promotes VDAC1 oligomerization to reprogram BCAA metabolism in tumor cells to polarize TAMs in LUAD.Cell death & disease · 2026Article
- Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion.Histology and histopathology · 2026Article
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- The USP1-WDR48 deubiquitinase complex functions as a molecular switch regulating tumor-associated macrophage activation and anti-tumor response.Cell death and differentiation · 2026Article
- Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical perspectives.Acta pharmaceutica Sinica. B · 2026Review
- Upregulation of ELP3 in acinar cells during acute pancreatitis is dispensable for homeostasis, inflammation, regeneration, and cancer initiation.Scientific reports · 2025Article
- Expressions, immune associations, and prognostic values of mitochondrial ribosomal protein MRPL3 in the pan cancer landscape.Discover oncology · 2025Article
- ALKBH8-mediated codon-specific translation promotes colorectal tumorigenesis.Nature communications · 2025Article
- Unconventional codon usage bias mediates mRNA translational dynamics in macrophages.PLoS biology · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- IGF2BP2: an mCellular & molecular biology letters · 2025Review
- Pan-cancer analysis identifies tRNA modification enzyme CTU2 as a novel tumor biomarker and its role in immune microenvironment.Frontiers in immunology · 2025Article
- The role of RNA modifications in disease-associated macrophages.Molecular therapy. Nucleic acids · 2024Review
- Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophage polarization is a process whereby macrophages acquire distinct effector states (M1 or M2) to carry out multiple and sometimes opposite functions. We show here that translational reprogramming occurs during macrophage polarization and that this relies on the Elongator complex subunit Elp3, an enzyme that modifies the wobble uridine base U34 in cytosolic tRNAs. Elp3 expression is downregulated by classical M1-activating signals in myeloid cells, where it limits the production of pro-inflammatory cytokines via FoxO1 phosphorylation, and attenuates experimental colitis in mice. In contrast, alternative M2-activating signals upregulate Elp3 expression through a PI3K- and STAT6-dependent signaling pathway. The metabolic reprogramming linked to M2 macrophage polarization relies on Elp3 and the translation of multiple candidates, including the mitochondrial ribosome large subunit proteins Mrpl3, Mrpl13, and Mrpl47. By promoting translation of its activator Ric8b in a codon-dependent manner, Elp3 also regulates mTORC2 activation. Elp3 expression in myeloid cells further promotes Wnt-driven tumor initiation in the intestine by maintaining a pool of tumor-associated macrophages exhibiting M2 features. Collectively, our data establish a functional link between tRNA modifications, mTORC2 activation, and macrophage polarization.
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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.