Stimulated expression of mRNAs in activated T cells depends on a functional CRM1 nuclear export pathway.
In metazoans, the nuclear export of bulk mRNAs is mediated by the export receptor TAP, together with its binding partner p15. A number of viral mRNAs, including the unspliced and partially spliced mRNA species of the human immunodeficiency virus (HIV), however, use an alternative export route via the importin beta-related export receptor CRM1. This raises the question of whether a subset of cellular mRNAs might be exported by CRM1 as well. To identify such mRNAs, we performed a systematic screen in different cell lines, using representational difference analyses of cDNA (cDNA-RDA). In HeLa and Cl-4 cells no cellular transcripts could be identified as exported via CRM1. In contrast, we found a number of CRM1-dependent mRNAs in Jurkat T cells, most of which are induced during a T cell response. One of the identified gene products, the dendritic cell marker CD83, was analyzed in detail. CD83 expression depends on a functional CRM1 pathway in activated Jurkat T cells as well as in a heterologous expression system, independent of activation. Our results point to an important role of the CRM1-dependent export pathway for the expression of CD83 and other genes under conditions of T cell activation.
University of Heidelberg, Department of Virology, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
Sylvia
S
Schütz
Jan
J
Chemnitz
Christiane
C
Spillner
Marcus
M
Frohme
Joachim
J
Hauber
Ralph H
RH
Kehlenbach
D021581:Active Transport, Cell Nucleus; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D015752:Genes, env; D006678:HIV / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D066298:In Vitro Techniques; D019169:Jurkat Cells; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen
D015703:Antigens, CD; D018076:DNA, Complementary; D007136:Immunoglobulins; D028884:Karyopherins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen