Prechtel Alexander T, Chemnitz Jan, Schirmer Susann, Ehlers Christina, Langbein-Detsch Ines, Stülke Jörg, Dabauvalle Marie-Christine, Kehlenbach Ralph H, Hauber Joachim
Heinrich Pette Institute for Experimental Virology and Immunology, D-20251 Hamburg, Germany.
J Biol Chem. 2006 Apr 21;281(16):10912-25. doi: 10.1074/jbc.M510306200. Epub 2006 Feb 16.
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.
树突状细胞是最有效的抗原呈递细胞，其特征是表面表达CD83。在此，我们表明CD83 mRNA的编码区包含一个新的顺式作用结构化RNA元件，该元件与HuR结合，HuR是富含AU元件的RNA结合蛋白ELAV家族的成员。哺乳动物细胞的瞬时转染表明，这种源自CD83 mRNA的元件在过表达HuR的细胞中作为转录后调控元件发挥作用。值得注意的是，HuR与CD83转录后调控元件的结合并不影响mRNA的稳定性。使用RNA干扰，我们表明HuR介导了CD83的有效表达。特别是，HuR是CD83转录本在细胞质中积累所必需的。同样，通过雷帕霉素B抑制CRM1核输出途径或过表达核孔蛋白Nup214/CAN的缺陷形式会降低细胞质中CD83 mRNA的水平。总之，所呈现的数据表明，在正常生理条件下，HuR-CRM1轴影响CD83 mRNA的核质转运。
