Transcriptomics,Genomics

Dataset Information

155

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


ABSTRACT: 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. Overall design: Determination of ZFP36 binding sites by HITS-CLIP in primary CD4+ T-cells at two time points post-activation (4 hours and 3 days)

INSTRUMENT(S): Illumina MiSeq (Mus musculus)

SUBMITTER: Robert Darnell 

PROVIDER: GSE96074 | GEO | 2018-03-01

REPOSITORIES: GEO

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Publications


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 mouse T cells, revealing unanticipated actions in regulating T-cell activation, proliferation, and effector functions. Transcriptome and ribosome profiling showed that ZFP36 represses mRNA target ab  ...[more]

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