Repression of major histocompatibility complex genes by a human trophoblast ribonucleic acid.
The suppression of polymorphic major histocompatibility complex antigen expression in human trophoblasts is critical for the avoidance of a cell-mediated immune response by maternal lymphocytes against cells expressing paternal antigens. In this study, a repressor of major histocompatibility complex gene expression was cloned by negative immunoselection using a trophoblast cDNA expression library in interferon-gamma-responsive human cells. The sequence of this regulatory gene was analyzed, and the functions of the transfected cDNA or microinjected gene product were examined in interferon-gamma-responsive cells by immunocytochemical methods. The repressor, called TSU-- trophoblast STAT (signal transducers and activators of transcription) utron (untranslated region of an mRNA)--reduced STAT1 nuclear translocation and suppressed major histocompatibility complex class II antigen expression at high doses of interferon-gamma and class I expression at low doses of interferon-gamma. TSU encoded a small, untranslated poly-A+-RNA that appeared to bind STAT1 through pairs of motifs analogous to STAT-binding promoter sequences. These promoter-like motifs, but no open reading frame, were conserved in a TSU-related gene in goats. Northern blot analysis demonstrated that TSU was expressed as a 0. 5-kilobase (kb) RNA in placenta and as an ubiquitous 4.4-kb RNA. TSU expression may protect trophoblasts from immune attack and promote the survival of the placenta and fetus.
Peyman
J A
JA
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. jpeyman@curagen.com
D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005805:Genes, MHC Class I / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008845:Microinjections; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012313:RNA / Q000008:administration & dosage; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014327:Trophoblasts / Q000737:chemistry*; D020506:Untranslated Regions
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D020506:Untranslated Regions; D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D007371:Interferon-gamma