title: HNRNPR Regulates the Expression of Classical and Nonclassical MHC Class I Proteins.
abstract: MHC class I molecules, in addition to their role in specific activation of the CTL of adaptive immune system, function also as the main ligands for NK cell inhibitory receptors, which prevent NK cells from killing normal, healthy cells. MHC class I proteins are divided into classical and nonclassical proteins. The former group consists of hundreds of HLA-A, B, and C alleles, which are universally expressed, whereas several alleles of the latter group, such as HLA-G, manifest a restricted expression pattern. Despite the important role played by these molecules in innate and adaptive immune responses, their complex expression regulation is not fully known. In our study, we investigated the regulation processes controlling the expression of MHC class I molecules, with a particular focus on their 3' untranslated regions. We identified heterogeneous nuclear ribonucleoprotein R (HNRNPR) as an important positive regulator of classical and nonclassical MHC class I molecules. HNRNPR is a RNA-binding protein belonging to the heterogeneous nuclear ribonucleoprotein family, which has a known role in processing of precursor mRNA. We demonstrated that HNRNPR binds MHC class I mRNAs in their 3' untranslated regions and enhances their stability and consequently their expression. Furthermore, regulation by HNRNPR modulates the cytotoxic activity of NK cells. In conclusion, we show that HNRNPR acts as a general positive regulator of MHC class I expression.
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and.
authors.forename: Adi
authors.initials: A
authors.lastname: Reches
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and.
authors.forename: Daphna
authors.identifier: 0000-0002-8489-9986
authors.initials: D
authors.lastname: Nachmani
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and.
authors.forename: Orit
authors.initials: O
authors.lastname: Berhani
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Duev-Cohen
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and.
authors.forename: Dorin
authors.initials: D
authors.lastname: Shreibman
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and.
authors.forename: Yael
authors.initials: Y
authors.lastname: Ophir
authors.affiliation: Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle (Saale), Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Institute of Medical Research Israel-Canada, Faculty of Medicine, Hebrew University Hadassah Medical School, 9112001 Jerusalem, Israel; and oferm@ekmd.huji.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D020413:3' Untranslated Regions; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D059951:HLA-G Antigens / Q000276:immunology; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; C439930:HNRNPR protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D055607:Receptors, Natural Killer Cell