title: MiRNA-mediated control of HLA-G expression and function.
abstract: HLA-G is a non-classical HLA class-Ib molecule expressed mainly by the extravillous cytotrophoblasts (EVT) of the placenta. The expression of HLA-G on these fetal cells protects the EVT cells from immune rejection and is therefore important for a healthy pregnancy. The mechanisms controlling HLA-G expression are largely unknown. Here we demonstrate that miR-148a and miR-152 down-regulate HLA-G expression by binding its 3'UTR and that this down-regulation of HLA-G affects LILRB1 recognition and consequently, abolishes the LILRB1-mediated inhibition of NK cell killing. We further demonstrate that the C/G polymorphism at position +3142 of HLA-G 3'UTR has no effect on the miRNA targeting of HLA-G. We show that in the placenta both miR-148a and miR-152 miRNAs are expressed at relatively low levels, compared to other healthy tissues, and that the mRNA levels of HLA-G are particularly high and we therefore suggest that this might enable the tissue specific expression of HLA-G.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, IMRIC, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Manaster
authors.forename: Debra
authors.initials: D
authors.lastname: Goldman-Wohl
authors.forename: Caryn
authors.initials: C
authors.lastname: Greenfield
authors.forename: Daphna
authors.initials: D
authors.lastname: Nachmani
authors.forename: Pinchas
authors.initials: P
authors.lastname: Tsukerman
authors.forename: Yaron
authors.initials: Y
authors.lastname: Hamani
authors.forename: Simcha
authors.initials: S
authors.lastname: Yagel
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D020413:3' Untranslated Regions; D015703:Antigens, CD / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D059951:HLA-G Antigens / Q000235:genetics* / Q000276:immunology*; D054502:Histocompatibility, Maternal-Fetal / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D035683:MicroRNAs / Q000235:genetics*; D011247:Pregnancy / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology; D014018:Tissue Distribution; D014327:Trophoblasts / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; D059951:HLA-G Antigens; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; C550570:MIRN148 microRNA, human; C550856:MIRN152 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D011971:Receptors, Immunologic