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Molecular and Cellular Biology, September 2005, p. 8139-8149, Vol. 25, No. 18
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.18.8139-8149.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

RNA-Binding Protein HuR Is Required for Stabilization of SLC11A1 mRNA and SLC11A1 Protein Expression

Yong Zhong Xu,¹ Sergio Di Marco,^1,2 Imed Gallouzi,² Marek Rola-Pleszczynski,³ and Danuta Radzioch^1*

McGill University Health Centre, McGill University, Department of Experimental Medicine and Department of Human Genetics, Montreal, QC, Canada,¹ McGill University, Department of Biochemistry, Montreal, QC, Canada,² University of Sherbrooke, Department of Pediatrics, Sherbrooke, QC, Canada³

Received 7 March 2005/ Returned for modification 15 April 2005/ Accepted 30 June 2005

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.

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* Corresponding author. Mailing address: McGill University, Departments of Experimental Medicine and Human Genetics, 1650 Cedar Avenue, L11-218, Montreal, QC, Canada H3G 1A4. Phone: (514) 934-1934, ext. 44517. Fax: (514) 934-8260. E-mail: danuta.radzioch{at}muhc.mcgill.ca.

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Molecular and Cellular Biology, September 2005, p. 8139-8149, Vol. 25, No. 18
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.18.8139-8149.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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