Dataset Information

Translational repression of pre-formed cytokine mRNA prevents chronic activation of memory T cells

ABSTRACT: Memory T cells are critical to protect us from recurring infections. Their instantaneous reactivity to pathogens is empowered by persistent expression of cytokine mRNA. How aberrant protein production of this pre-formed mRNA is prevented in the absence of infection, however, remains unresolved. We show that protein production in memory T cells is blocked through a 3’untranslated region (3’UTR)-mediated process, and that AU-rich elements (AREs) are key herein. Germ-line deletion of AREs leads to chronic IFN- production in bona fide memory T cells. Strikingly, the aberrant protein production does not result from increased mRNA levels and/or half-life. Rather, AREs block the recruitment of cytokine mRNA to ribosomes, a process that is mediated by the ARE-binding protein ZFP36L2. Thus, AREs are crucial elements for translational repression that allow murine and human memory T cells to contain pre-formed cytokine mRNAs, while preventing undesirable protein production in the absence of infection.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, T Cell

SUBMITTER: Maartje van den Biggelaar

LAB HEAD: Maartje van den Biggelaar

PROVIDER: PXD008051 | Pride | 2018-05-15

REPOSITORIES: Pride

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Translational repression of pre-formed cytokine-encoding mRNA prevents chronic activation of memory T cells.

Salerno Fiamma F Engels Sander S van den Biggelaar Maartje M van Alphen Floris P J FPJ Guislain Aurelie A Zhao Wanqi W Hodge Deborah L DL Bell Sarah E SE Medema Jan Paul JP von Lindern Marieke M Turner Martin M Young Howard A HA Wolkers Monika C MC

Nature immunology 20180709 8

Memory T cells are critical for the immune response to recurring infections. Their instantaneous reactivity to pathogens is empowered by the persistent expression of cytokine-encoding mRNAs. How the translation of proteins from pre-formed cytokine-encoding mRNAs is prevented in the absence of infection has remained unclear. Here we found that protein production in memory T cells was blocked via a 3' untranslated region (3' UTR)-mediated process. Germline deletion of AU-rich elements (AREs) in th ...[more]

PMID: 29988089

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