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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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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. |
format | Online Article Text |
id | pubmed-3338430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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