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
Organism
Number of Samples 10
Release Date 2020/07/24 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP273454
ENA SRP273454
GEO GSE155087
BioProject PRJNA648398

Publication

Title
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)
SRR12318326 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318327 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318328 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318329 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318330 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318331 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318332 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318333 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318334 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
SRR12318335 PRJNA648398 Mus musculus CD4+ T cells Ribo-Seq
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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