ArticleThe Journal of experimental medicine2025
tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- RNA modifications in cancer: regulators of tumor evolution and therapeutic response.Molecular cancer · 2026Review
- tRNA mEMBO reports · 2026Article
- The RNA methylation modification as an immunometabolic regulatory hub in pancreatic cancer: from mechanistic insights to clinical translation perspectives.Molecular cancer · 2026Review
- Deciphering Hierarchical Transcriptional Control of Fatty Acid Metabolism in Megalobrama Amblycephala: Insights from Promoter Architecture, PPAR Synergy, and Network Biology.Marine biotechnology (New York, N.Y.) · 2026Article
- Pseudouridine synthases upregulate 5'-tRF-Lys to inhibit YPEL3 and drive malignant progression in nasopharyngeal carcinoma.Cellular & molecular biology letters · 2026Article
- TRMT6/TRMT61A-mediated tRNA mCellular & molecular biology letters · 2026Article
- Insights Into circRNA-Mediated Lipid Metabolism in Cancer Progression.Journal of cellular and molecular medicine · 2026Review
- Epitranscriptomic control of cancer hallmarks: Functions, mechanisms, and therapeutics of RNA modifications.Cancer cell · 2026Review
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- ENSURE: the encyclopedia of suppressor tRNA with an AI assistant.Nucleic acids research · 2026Article
- Epitranscriptomic control of epithelial-mesenchymal transition in cancer: mechanisms, plasticity, and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- RNA epitranscriptomic regulation of tumor immune evasion: mechanisms, context-dependent roles, and therapeutic implications.Frontiers in immunology · 2026Review
- RNA Modifications in T cell Immunity: Mechanisms, Disease Relevance, and Therapeutic Potential.Theranostics · 2026Review
- LPCAT1 as a prognostic biomarker and risk indicator for hepatocellular carcinoma: insights into genes related to lipid metabolism.Frontiers in oncology · 2026Article
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- RNA modifications: roles in immune cell biology and tumor regulation.Cancer cell international · 2025Review
- RNA methylation in hepatocellular carcinoma: from metabolic reprogramming and immune escape mechanisms to small molecule inhibitor development.Journal of translational medicine · 2025Review
- Non-Coding RNAs as Critical Modulators of Cholesterol Metabolism in Cancer.Biomedicines · 2025Review
- Epitranscriptomics Regulation of CD70, CD80, and TIGIT in Cancer Immunity.International journal of molecular sciences · 2025Article
- The role of m5C, m1A and m7G modifications in tumors of urinary system.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
Activation of CD8+ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands of effector functions. However, the posttranscriptional mechanisms underpinning this process remain obscure. The transfer RNA (tRNA) N1-methyladenine (m1A) modification, essential for tRNA stability and protein translation, has an undefined physiological function in CD8+ T cells, particularly in antitumor responses. Here, we demonstrate that the tRNA m1A "writer" gene Trmt61a enhances the tumor-killing capacity of CD8+ T cells by regulating cholesterol biosynthesis. Deletion of Trmt61a in CD8+ T cells leads to a compromised tumor-killing function in both in vivo and in vitro assays. Mechanistically, tRNA m1A promotes antitumor immunity in CD8+ T cells by enhancing the translation of ATP citrate lyase, a key enzyme for cholesterol biosynthesis. Cholesterol supplementation rescues the impaired tumor-killing function and proliferation of TRMT61A-deficient CD8+ T cells. Our findings highlight tRNA m1A modification as a regulatory checkpoint in cholesterol metabolism in CD8+ T cells, suggesting potential novel strategies for cancer immunotherapy.
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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.