Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element

doi:10.1074/jbc.M510306200

Expression of CD83 Is Regulated by HuR via a Novel cis-Active Coding Region RNA Element*

^‡Heinrich Pette Institute for Experimental Virology and Immunology, D-20251 Hamburg, Germany, the ^§Institute of Microbiology, Biochemistry, and Genetics, University Erlangen-Nürnberg, D-91054 Erlangen, Germany, the ^¶Institute for Microbiology and Genetics, University of Göttingen, D-37077 Göttingen, Germany, the ^∥Department of Cell and Developmental Biology, Biocenter of the University of Würzburg, D-97074 Würzburg, Germany, and the ^**Center of Biochemistry and Molecular Cell Biology, University of Göttingen, D-37073 Göttingen, Germany

2 To whom correspondence should be addressed: Heinrich Pette Inst. for Experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany. Tel.: 49-40-4805-1241; Fax: 49-40-4805-1184; E-mail: joachim.hauber{at}hpi.uni-hamburg.de.

Abstract

Dendritic cells are the most potent of the antigen-presenting cells and are characterized by surface expression of CD83. Here, we show that the coding region of CD83 mRNA contains a novel cis-acting structured RNA element that binds to HuR, a member of the ELAV family of AU-rich element RNA-binding proteins. Transient transfection of mammalian cells demonstrated that this CD83 mRNA-derived element acts as a post-transcriptional regulatory element in cells overexpressing HuR. Notably, binding of HuR to the CD83 post-transcriptional regulatory element did not affect mRNA stability. Using RNA interference, we show that HuR mediated efficient expression of CD83. In particular, HuR was required for cytoplasmic accumulation of CD83 transcripts. Likewise, inhibition of the CRM1 nuclear export pathway by leptomycin B or overexpression of a defective form of the nucleoporin Nup214/CAN diminished cytoplasmic CD83 mRNA levels. In summary, the data presented demonstrate that the HuR-CRM1 axis affects the nucleocytoplasmic translocation of CD83 mRNA under regular physiological conditions.

Footnotes

↵3 The abbreviations used are: DCs, dendritic cells; ERG, early response gene; AREs, AU-rich elements; UTR, untranslated region; RNP, ribonucleoprotein; TNF-α, tumor necrosis factor-α; HIV-1, human immunodeficiency virus type 1; GST, glutathione S-transferase; siRNA, small interfering RNA; nt, nucleotides; SL, stem-loop; FACS, fluorescence-activated cell sorter; PMA, phorbol 12-myristate 13-acetate; RT, reverse transcription; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PRE, post-transcriptional regulatory element.
↵* This work was supported by Wilhelm Sander Stiftung Grant 2003.033.1. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵1 Both authors contributed equally to this work.
- Received September 20, 2005.
- Revision received January 23, 2006.
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