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- Title
MiRNA-Mediated Control of HLA-G Expression and Function.
- Authors
Manaster, Irit; Goldman-Wohl, Debra; Greenfield, Caryn; Nachmani, Daphna; Tsukerman, Pinchas; Hamani, Yaron; Yagel, Simcha; Mandelboim, Ofer
- 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 39UTR 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 39UTR 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.
- Subjects
GRAVID uterus; PLACENTA; KILLER cells; MESSENGER RNA; GENE expression; HLA histocompatibility antigens; PREGNANCY
- Publication
PLoS ONE, 2012, Vol 7, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0033395