1. MiRNA-mediated control of HLA-G expression and function.
- Author
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Manaster I, Goldman-Wohl D, Greenfield C, Nachmani D, Tsukerman P, Hamani Y, Yagel S, and Mandelboim O
- Subjects
- 3' Untranslated Regions, Antigens, CD immunology, Base Sequence, Cell Line, Down-Regulation, Female, Histocompatibility, Maternal-Fetal genetics, Histocompatibility, Maternal-Fetal immunology, Humans, Killer Cells, Natural immunology, Leukocyte Immunoglobulin-like Receptor B1, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Immunologic immunology, Tissue Distribution, Trophoblasts immunology, HLA-G Antigens genetics, HLA-G Antigens immunology, MicroRNAs genetics, Pregnancy genetics, Pregnancy immunology
- 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.
- Published
- 2012
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