Warshauer Emily, Samuelov Liat, Sarig Ofer, Vodo Dan, Bindereif Albrecht, Kanaan Moien, Gat Uri, Fuchs-Telem Dana, Shomron Noam, Farberov Luba, Pasmanik-Chor Metsada, Nardini Gil, Winkler Eyal, Meilik Benjamin, Petit Isabelle, Aberdam Daniel, Paus Ralf, Sprecher Eli, Nousbeck Janna
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.
Exp Dermatol. 2015 Aug;24(8):618-22. doi: 10.1111/exd.12737. Epub 2015 May 26.
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.
脱发-神经缺陷-内分泌病（ANE）综合征是一种罕见的遗传性毛发疾病，研究表明其由RNA结合基序蛋白28（RBM28）表达降低所致。在本研究中，我们试图阐明RBM28在毛发生物学中的作用。首先，我们试图获取RBM28直接参与头发生长的证据。当在人毛囊（HF）器官培养物中下调RBM28时，我们观察到毛囊生长期诱导和HF生长停滞，表明RBM28是正常头发生长所必需的。我们还旨在鉴定RBM28的分子靶点。鉴于最近发现一种RBM28同源物在秀丽隐杆线虫中调节miRNA生物合成，且鉴于miRNA对毛囊正常发育具有已知的关键重要性，我们研究了RBM28敲低细胞中的整体miRNA表达谱。该分析表明RBM28控制miR-203的表达。发现miR-203继而调节编码转录因子p63的TP63，p63对毛发形态发生至关重要。总之，RBM28通过调节miR-203和p63活性对头发生长调节起作用。
