Format

Send to

Choose Destination
Nat Commun. 2018 Mar 20;9(1):1145. doi: 10.1038/s41467-018-03326-5.

ZFR coordinates crosstalk between RNA decay and transcription in innate immunity.

Author information

1
Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Room 2341, Bethesda, MD, 20892, USA. nazmul.haque@nih.gov.
2
Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Drive, Room 2A01, Bethesda, MD, 20892, USA.
3
Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Room 2341, Bethesda, MD, 20892, USA. j.hogg@nih.gov.

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.

PMID:
29559679
PMCID:
PMC5861047
DOI:
10.1038/s41467-018-03326-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center