Expression of CD83 is regulated by HuR via a novel cis-active coding region RNA element.
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.
Prechtel
Alexander T
AT
Heinrich Pette Institute for Experimental Virology and Immunology, D-20251 Hamburg, Germany.
Chemnitz
Jan
J
Schirmer
Susann
S
Ehlers
Christina
C
Langbein-Detsch
Ines
I
Stülke
Jörg
J
Dabauvalle
Marie-Christine
MC
Kehlenbach
Ralph H
RH
Hauber
Joachim
J
D021581:Active Transport, Cell Nucleus; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D007136:Immunoglobulins / Q000096:biosynthesis*; D047468:Immunoprecipitation; D019169:Jurkat Cells; D028884:Karyopherins / Q000502:physiology*; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D014176:Protein Biosynthesis; D021381:Protein Transport; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen
D015703:Antigens, CD; D000954:Antigens, Surface; D018076:DNA, Complementary; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005231:Fatty Acids, Unsaturated; D005982:Glutathione Transferase; D007136:Immunoglobulins; D028884:Karyopherins; D008156:Luciferases; D008562:Membrane Glycoproteins; D028861:Nuclear Pore Complex Proteins; D012313:RNA; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen; C098770:ELAVL1 protein, human; C085914:NUP214 protein, human; C038753:leptomycin B