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Exp Dermatol. 2015 Aug;24(8):618-22. doi: 10.1111/exd.12737. Epub 2015 May 26.

RBM28, a protein deficient in ANE syndrome, regulates hair follicle growth via miR-203 and p63.

Author information

1
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
2
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
3
Institute of Biochemistry, Justus Liebig University of Giessen, Heinrich-Buff-Ring, Giessen, Germany.
4
Department of Life Sciences, Bethlehem University, Bethlehem, Palestine.
5
Department of Cell and Developmental Biology, The Hebrew University, Jerusalem, Israel.
6
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
7
The Bioinformatics Unit, The Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
8
Department of Plastic and Reconstructive Surgery, The Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel.
9
Department of Plastic and Reconstructive Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
10
INSERM UMR-S976, Hôpital Saint-Louis, Paris, France.
11
Université Paris-Diderot, Paris, France.
12
Department of Dermatology, University of Luebeck, Luebeck, Germany.

Abstract

Alopecia-neurological defects-endocrinopathy (ANE) syndrome is a rare inherited hair disorder, which was shown to result from decreased expression of the RNA-binding motif protein 28 (RBM28). In this study, we attempted to delineate the role of RBM28 in hair biology. First, we sought to obtain evidence for the direct involvement of RBM28 in hair growth. When RBM28 was downregulated in human hair follicle (HF) organ cultures, we observed catagen induction and HF growth arrest, indicating that RBM28 is necessary for normal hair growth. We also aimed at identifying molecular targets of RBM28. Given that an RBM28 homologue was recently found to regulate miRNA biogenesis in C. elegans and given the known pivotal importance of miRNAs for proper hair follicle development, we studied global miRNA expression profile in cells knocked down for RBM28. This analysis revealed that RBM28 controls the expression of miR-203. miR-203 was found to regulate in turn TP63, encoding the transcription factor p63, which is critical for hair morphogenesis. In conclusion, RBM28 contributes to HF growth regulation through modulation of miR-203 and p63 activity.

KEYWORDS:

RBM28; alopecia; hair follicle; miR-203; p63

PMID:
25939713
DOI:
10.1111/exd.12737
[Indexed for MEDLINE]

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