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Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression.

Authors
  • Rg, De Bruin
  • L, Shiue
  • J, Prins
  • Hc, De Boer
  • A, Singh
  • Ws, Fagg
  • Jm, Van Gils
  • Jm, Duijs
  • S, Katzman
  • Ao, Kraaijeveld
  • S, Böhringer
  • Wy, Leung
  • Sm, Kielbasa
  • Jp, Donahue
  • Ph, Van Der Zande
  • R, Sijbom
  • Cm, Van Alem
  • I, Bot
  • C, Van Kooten
  • Jw, Jukema
  • And 7 more
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Volume
7
Identifiers
DOI: 10.1038/ncomms10846
Source
UCSC Bioinformatics biomedical-ucsc
License
Unknown

Abstract

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.

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