RNA-binding protein HuR is required for stabilization of SLC11A1 mRNA and SLC11A1 protein expression

Yong Zhong Xu, Sergio Di Marco, Imed Gallouzi, Marek Rola-Pleszczynski, Danuta Radzioch

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The solute carrier family 11 member 1 (SLC11A1, formerly NRAMP1) gene is associated with infectious and autoimmune diseases and plays an important role in macrophage activation. Human SLC11A1 mRNA contains an AU-rich element (ARE) within the 3′ untranslated region; however, its role in the regulation of SLC11A1 gene expression has not been elucidated. Here we analyze the expression of SLC11A1 in human monocytes and HL-60 cells and then use HL-60 cells as a model to determine whether RNA-binding protein HuR is associated with the ARE and involved in SLC11A1 mRNA turnover. Our results demonstrate a binding of HuR to the SLC11A1 ARE in phorbol myristate acetate (PMA)-differentiated cells dramatically increased compared to that in undifferentiated cells. Interestingly, PMA-induced accumulation of cytoplasmic HuR occurs in parallel with an increase in the binding of HuR to SLC11A1 ARE and with an increase in the SLC11A1 mRNA level. This suggests that HuR's cytoplasmic localization plays an important role in the regulation of SLC11A1 expression. We also observe that down-regulation of HuR expression by RNA interference (RNAi) results in a decrease in SLC11A1 expression which can be restored by the addition of recombinant HuR protein to the RNAi-treated cells. Finally, we show that HuR overexpression in HL-60 cells significantly increases the SLC11A1 mRNA stability. Taken together, our data demonstrate that HuR is a key mediator of posttranscriptional regulation and expression of the SLC11A1 gene.

Original languageEnglish
Pages (from-to)8139-8149
Number of pages11
JournalMolecular and Cellular Biology
Volume25
Issue number18
DOIs
Publication statusPublished - Sep 2005
Externally publishedYes

Fingerprint

AU Rich Elements
RNA-Binding Proteins
HL-60 Cells
Messenger RNA
Gene Expression Regulation
Tetradecanoylphorbol Acetate
RNA Interference
Macrophage Activation
RNA Stability
3' Untranslated Regions
Recombinant Proteins
Autoimmune Diseases
Communicable Diseases
Monocytes
Down-Regulation
natural resistance-associated macrophage protein 1
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

RNA-binding protein HuR is required for stabilization of SLC11A1 mRNA and SLC11A1 protein expression. / Xu, Yong Zhong; Di Marco, Sergio; Gallouzi, Imed; Rola-Pleszczynski, Marek; Radzioch, Danuta.

In: Molecular and Cellular Biology, Vol. 25, No. 18, 09.2005, p. 8139-8149.

Research output: Contribution to journalArticle

Xu, Yong Zhong ; Di Marco, Sergio ; Gallouzi, Imed ; Rola-Pleszczynski, Marek ; Radzioch, Danuta. / RNA-binding protein HuR is required for stabilization of SLC11A1 mRNA and SLC11A1 protein expression. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 18. pp. 8139-8149.
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