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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis

ABSTRACT: An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis

PROVIDER: PRJNA1023901 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25594415_1.fastq.gz	Fastqsanger.gz
	SRR25594415_2.fastq.gz	Fastqsanger.gz
	SRR25594416_1.fastq.gz	Fastqsanger.gz
	SRR25594416_2.fastq.gz	Fastqsanger.gz
	SRR25594417_1.fastq.gz	Fastqsanger.gz

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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [bulk RNA-seq]

Project description:An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [bulk RNA-seq]

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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [single cell RNA-seq]

Project description:An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [single cell RNA-seq]

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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [bulk RNA-seq]

Project description:T regulatory (Treg) cells play an essential role in suppressing the response of immune effector cells. The zinc finger protein 36 (ZFP36) family of RNA binding proteins (RBP) have been demonstrated to have crucial roles in development, stress responses and inflammation. Treg-restricted deletion of ZFP36L1 leads to a loss of immune homeostasis with an expansion of effector cell subsets and over-production of inflammatory cytokines, with the phenotype exacerbated with the combined deletion of ZFP36L2. Single cell RNA seq analyses revealed a Treg transcriptional profile that was biased towards an activated phenotype. We report that ZFP36L1 and ZFP36L2 play a key role in regulating Treg sensitivity to cytokine signalling. By limiting the IFNg signalling pathway these RBP influence Th-type cell transcriptional programs and promote Treg responsiveness to IL-2 and IL-7. Together our results reveal cell intrinsic effects of these RBP important for Treg function.

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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis [single cell RNA-seq]

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An essential role for ZFP36 RNA-binding proteins in regulatory T cells reinforces immune homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-08-08 | GSE244621 | GEO

ZFP36 RNA binding proteins restrain T-cell activation and anti-viral immunity [HITS-CLIP]

Project description:Dynamic post-transcriptional control of RNA expression by RNA-binding proteins (RBPs) is critical during immune response. ZFP36 RBPs are prominent inflammatory regulators linked to autoimmunity and cancer, but functions in adaptive immunity are less clear. We used HITS-CLIP to define ZFP36 targets in T-cells, which confirmed regulation of cytokine expression and revealed unanticipated actions in regulating T-cell activation and proliferation. Transcriptome and ribosome profiling showed that ZFP36 represses mRNA target abundance and translation, most robustly through a novel class of AU-rich sites in coding sequence. Functional studies revealed that ZFP36 regulates early T-cell activation kinetics by attenuating activation marker expression, limiting T-cell expansion, and promoting apoptosis in a cell autonomous manner. Strikingly, loss of ZFP36 in vivo accelerated T-cell responses to acute viral infection, and enhanced anti-viral immunity. These findings uncover a critical role for ZFP36 RBPs in restraining T-cell expansion and effector functions, and suggest ZFP36 inhibition as a novel strategy to enhance immune-based therapies.

2018-03-01 | GSE96074 | GEO

ZFP36 RNA binding proteins restrain T-cell activation kinetics and anti-viral immunity [ribo-seq]

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ZFP36 RNA binding proteins restrain T-cell activation kinetics and anti-viral immunity [RNA-seq]

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Global Target mRNA Specification and Regulation by RNA-Binding Protein ZFP36/Tristetraprolin/TTP [PAR-CLIP]

Project description:Tristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3M-bM-^@M-^Y UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins. FLAG-HA ZFP36

2013-12-24 | E-GEOD-53184 | biostudies-arrayexpress

Global Target mRNA Specification and Regulation by RNA-Binding Protein ZFP36/Tristetraprolin/TTP [Affymetrix]

2013-12-24 | E-GEOD-53183 | biostudies-arrayexpress