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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 07, 2025 |
| Title |
tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Activation of CD8+ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands of their effector functions. However, the post-transcriptional mechanisms underpinning this process remain obscure. The tRNA N1-methyladenine (m1A) modification, which plays a role in maintaining tRNA stability and modulating 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. We find that Trmt61a expression in CD8+ T cells is upregulated upon activation and correlates positively with T cell-mediated cytotoxicity within the tumor microenvironment of colorectal cancer (CRC) patients. Deletion of Trmt61a in CD8+ T cells leads to a compromised tumor-killing function in both in vivo and in vitro assays, which is dependent on the m1A catalytic activity of TRMT61A. Mechanistically, tRNA m1A promotes antitumor immunity in CD8+ T cells by enhancing the translation of ATP citrate lyase (ACLY), a key enzyme for cholesterol biosynthesis. Supplementation with cholesterol can rescue the impaired tumor-killing function and proliferation of TRMT61A-deficient CD8+ T cells. Our findings underscore the significance of 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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| Overall design |
For RNA-seq, there are 0h,48h for WT samples and 0h,48h for Trmt61A-cKO samples.
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| Contributor(s) |
Miao S, Li H, Song X, Liu Y, Wang G, Kan C, Ye Y, Liu R, Li H |
| Citation(s) |
39873720 |
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| Submission date |
Aug 24, 2024 |
| Last update date |
Apr 08, 2025 |
| Contact name |
Xiaohan Song |
| E-mail(s) |
aurorasxh@sjtu.edu.cn
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| Phone |
13515207000
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| Organization name |
Shanghai Jiao Tong University School of Medicine
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| Street address |
South ChongQing Road 227
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| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200025 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1152006 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE275602_TRMT61a_CD8_counts_anno.xlsx |
4.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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