作者: Michael J Moore , Nathalie E Blachere , John J Fak , Christopher Y Park , Kirsty Sawicka
DOI: 10.7554/ELIFE.33057
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摘要: 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 less clear. We used HITS-CLIP define targets mouse T cells, revealing unanticipated actions regulating T-cell activation, proliferation, effector functions. Transcriptome ribosome profiling showed that represses mRNA target abundance translation, notably through novel AU-rich sites coding sequence. Functional studies revealed regulates early activation kinetics cell autonomously, attenuating marker expression, limiting expansion, promoting apoptosis. Strikingly, loss vivo accelerated responses acute viral infection enhanced anti-viral immunity. These findings uncover a role for restraining expansion functions, suggest inhibition as strategy enhance immune-based therapies.