RBM28, a protein deficient in ANE syndrome, regulates hair follicle growth via miR-203 and p63.
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.
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Emily
E
Warshauer
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Liat
L
Samuelov
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Ofer
O
Sarig
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Dan
D
Vodo
Institute of Biochemistry, Justus Liebig University of Giessen, Heinrich-Buff-Ring, Giessen, Germany.
Albrecht
A
Bindereif
Department of Life Sciences, Bethlehem University, Bethlehem, Palestine.
Moien
M
Kanaan
Department of Cell and Developmental Biology, The Hebrew University, Jerusalem, Israel.
Uri
U
Gat
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Dana
D
Fuchs-Telem
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Noam
N
Shomron
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Luba
L
Farberov
The Bioinformatics Unit, The Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Metsada
M
Pasmanik-Chor
Department of Plastic and Reconstructive Surgery, The Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel.
Gil
G
Nardini
Department of Plastic and Reconstructive Surgery, The Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan, Israel.
Eyal
E
Winkler
Department of Plastic and Reconstructive Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Benjamin
B
Meilik
INSERM UMR-S976, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Paris, France.
Isabelle
I
Petit
INSERM UMR-S976, Hôpital Saint-Louis, Paris, France.|Université Paris-Diderot, Paris, France.
Daniel
D
Aberdam
Department of Dermatology, University of Luebeck, Luebeck, Germany.
Ralf
R
Paus
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Eli
E
Sprecher
Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Janna
J
Nousbeck
D000505:Alopecia / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D004700:Endocrine System Diseases / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006197:Hair / Q000254:growth & development; D018859:Hair Follicle / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000378:metabolism* / Q000503:physiopathology; D015603:Keratinocytes / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D009024:Morphogenesis; D009924:Organ Culture Techniques; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D015854:Up-Regulation
C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C530063:RBM28 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
RBM28; alopecia; hair follicle; miR-203; p63