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ZFR coordinates crosstalk between RNA decay and transcription in innate immunity

Author

Listed:
  • Nazmul Haque

    (National Institutes of Health)

  • Ryota Ouda

    (National Institutes of Health)

  • Chao Chen

    (National Institutes of Health)

  • Keiko Ozato

    (National Institutes of Health)

  • J. Robert Hogg

    (National Institutes of Health)

Abstract

Control of type I interferon production is crucial to combat infection while preventing deleterious inflammatory responses, but the extent of the contribution of post-transcriptional mechanisms to innate immune regulation is unclear. Here, we show that human zinc finger RNA-binding protein (ZFR) represses the interferon response by regulating alternative pre-mRNA splicing. ZFR expression is tightly controlled during macrophage development; monocytes express truncated ZFR isoforms, while macrophages induce full-length ZFR to modulate macrophage-specific alternative splicing. Interferon-stimulated genes are constitutively activated by ZFR depletion, and immunostimulation results in hyper-induction of interferon β (IFNβ/IFNB1). Through whole-genome analyses, we show that ZFR controls interferon signaling by preventing aberrant splicing and nonsense-mediated decay of histone variant macroH2A1/H2AFY mRNAs. Together, our data suggest that regulation of ZFR in macrophage differentiation guards against aberrant interferon responses and reveal a network of mRNA processing and decay that shapes the transcriptional response to infection.

Suggested Citation

  • Nazmul Haque & Ryota Ouda & Chao Chen & Keiko Ozato & J. Robert Hogg, 2018. "ZFR coordinates crosstalk between RNA decay and transcription in innate immunity," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03326-5
    DOI: 10.1038/s41467-018-03326-5
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