Matheson et al. 2021 (PRJNA648398)
General Details
| Title | Multiomics analysis couples mRNA turnover and translational control of glutamine metabolism to the differentiation of the activated CD4+ T cell |
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| Organism | |
| Number of Samples | 10 |
| Release Date | 2020/07/24 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP273454 |
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| ENA | SRP273454 |
| GEO | GSE155087 |
| BioProject | PRJNA648398 |
Publication
| Title | |
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| Authors | Matheson LS, Petkau G, Sáenz-Narciso B, D'Angeli V, McHugh J, Newman R, Munford H, West J, Chakraborty K, Roberts J, Łukasiak S, Díaz-Muñoz MD, Bell SE, Dimeloe S, Turner M |
| Journal | Scientific reports |
| Publication Date | 2022 Nov 16 |
| Abstract | The ZFP36 family of RNA-binding proteins acts post-transcriptionally to repress translation and promote RNA decay. Studies of genes and pathways regulated by the ZFP36 family in CD4 + T cells have focussed largely on cytokines, but their impact on metabolic reprogramming and differentiation is unclear. Using CD4 + T cells lacking Zfp36 and Zfp36l1, we combined the quantification of mRNA transcription, stability, abundance and translation with crosslinking immunoprecipitation and metabolic profiling to determine how they regulate T cell metabolism and differentiation. Our results suggest that ZFP36 and ZFP36L1 act directly to limit the expression of genes driving anabolic processes by two distinct routes: by targeting transcription factors and by targeting transcripts encoding rate-limiting enzymes. These enzymes span numerous metabolic pathways including glycolysis, one-carbon metabolism and glutaminolysis. Direct binding and repression of transcripts encoding glutamine transporter SLC38A2 correlated with increased cellular glutamine content in ZFP36/ZFP36L1-deficient T cells. Increased conversion of glutamine to α-ketoglutarate in these cells was consistent with direct binding of ZFP36/ZFP36L1 to Gls (encoding glutaminase) and Glud1 (encoding glutamate dehydrogenase). We propose that ZFP36 and ZFP36L1 as well as glutamine and α-ketoglutarate are limiting factors for the acquisition of the cytotoxic CD4 + T cell fate. Our data implicate ZFP36 and ZFP36L1 in limiting glutamine anaplerosis and differentiation of activated CD4 + T cells, likely mediated by direct binding to transcripts of critical genes that drive these processes. © 2022. The Author(s). |
| PMC | PMC9669047 |
| PMID | 36385275 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR12318326 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 |  |
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| SRR12318327 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318328 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318329 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318330 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318331 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318332 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318333 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318334 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| SRR12318335 | PRJNA648398 | Mus musculus | CD4 | Ribo-Seq | 0.0 | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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