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The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation

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...

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Autores principales: Fu, Haiyan, Yang, Guodong, Wei, Mengying, Liu, Li, Jin, Liang, Lu, Xiaozhao, Wang, Li, Shen, Lan, Zhang, Jing, Lu, Huanyu, Yao, Libo, Lu, Zifan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338430/
https://www.ncbi.nlm.nih.gov/pubmed/22398723
http://dx.doi.org/10.1091/mbc.E11-05-0412
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author Fu, Haiyan
Yang, Guodong
Wei, Mengying
Liu, Li
Jin, Liang
Lu, Xiaozhao
Wang, Li
Shen, Lan
Zhang, Jing
Lu, Huanyu
Yao, Libo
Lu, Zifan
author_facet Fu, Haiyan
Yang, Guodong
Wei, Mengying
Liu, Li
Jin, Liang
Lu, Xiaozhao
Wang, Li
Shen, Lan
Zhang, Jing
Lu, Huanyu
Yao, Libo
Lu, Zifan
author_sort Fu, Haiyan
collection PubMed
description 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.
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spelling pubmed-33384302012-07-16 The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation Fu, Haiyan Yang, Guodong Wei, Mengying Liu, Li Jin, Liang Lu, Xiaozhao Wang, Li Shen, Lan Zhang, Jing Lu, Huanyu Yao, Libo Lu, Zifan Mol Biol Cell Articles 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. The American Society for Cell Biology 2012-05-01 /pmc/articles/PMC3338430/ /pubmed/22398723 http://dx.doi.org/10.1091/mbc.E11-05-0412 Text en © 2012 Fu et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Fu, Haiyan
Yang, Guodong
Wei, Mengying
Liu, Li
Jin, Liang
Lu, Xiaozhao
Wang, Li
Shen, Lan
Zhang, Jing
Lu, Huanyu
Yao, Libo
Lu, Zifan
The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation
title The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation
title_full The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation
title_fullStr The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation
title_full_unstemmed The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation
title_short The RNA-binding protein QKI5 is a direct target of C/EBPα and delays macrophage differentiation
title_sort rna-binding protein qki5 is a direct target of c/ebpα and delays macrophage differentiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338430/
https://www.ncbi.nlm.nih.gov/pubmed/22398723
http://dx.doi.org/10.1091/mbc.E11-05-0412
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