title: The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation.
abstract: Differentiated macrophages are essential for the innate immune system; however, the molecular mechanisms underlying the generation of macrophages remain largely unknown. Here we show that the RNA-binding protein QKI, mainly QKI-5, is transcriptionally activated in the early differentiated monocytic progenitors when CCAAT/enhancer-binding protein (C/EBP) α is expressed. The forced expression of C/EBPα increases the endogenous expression of QKI. Chromatin immunoprecipitation analysis and reporter assays further confirm that C/EBPα activates the transcription of QKI, primarily by binding to the distal C/EBPα-binding site. Blocking the induction of QKI using RNA interference enhances the expression of endogenous CSF1R and facilitates macrophage differentiation. Further study of the mechanism reveals that QKI-5 facilitates the degradation of CSF1R mRNA by interacting with the distal QRE in the 3' untranslated region. In summary, we show that in committed macrophage progenitors, C/EBPα-activated QKI-5 negatively regulates macrophage differentiation by down-regulating CSF1R expression, forming a negative feedback loop during macrophage differentiation.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Mgilitary Medical University, 710032 Xi'an, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Fu
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
authors.forename: Mengying
authors.initials: M
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Huanyu
authors.initials: H
authors.lastname: Lu
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Zifan
authors.initials: Z
authors.lastname: Lu
mesh_terms: D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D015536:Down-Regulation; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C490832:QKI protein, human; D016601:RNA-Binding Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor