Human skin specific long noncoding RNA HOXC13-AS regulates epidermal differentiation by interfering with Golgi-ER retrograde transport

作者：Letian Zhang, Minna Piipponen, Zhuang Liu, Dongqing Li, Xiaowei Bian, Guanglin Niu, Jennifer Geara, Maria A. Toma, Pehr Sommar, Ning Xu · 发表于：Cell Death and Differentiation · 年份：2023 · DOI：10.1038/s41418-023-01142-z · 被引用次数：17 · 研究领域：Cancer-related molecular mechanisms research、RNA regulation and disease、Plant and Fungal Interactions Research

After a skin injury, keratinocytes switch from a state of homeostasis to one of regeneration leading to the reconstruction of the epidermal barrier. The regulatory mechanism of gene expression underpinning this key switch during human skin wound healing is enigmatic. Long noncoding RNAs (lncRNAs) constitute a new horizon in the understanding of the regulatory programs encoded in the mammalian genome. By comparing the transcriptome of an acute human wound and skin from the same donor as well as keratinocytes isolated from these paired tissue samples, we generated a list of lncRNAs showing changed expression in keratinocytes during wound repair. Our study focused on HOXC13-AS, a recently evolved human lncRNA specifically expressed in epidermal keratinocytes, and we found that its expression was temporally downregulated during wound healing. In line with its enrichment in suprabasal keratinocytes, HOXC13-AS was found to be increasingly expressed during keratinocyte differentiation, but its expression was reduced by EGFR signaling. After HOXC13-AS knockdown or overexpression in human primary keratinocytes undergoing differentiation induced by cell suspension or calcium treatment and in organotypic epidermis, we found that HOXC13-AS promoted keratinocyte differentiation. Moreover, RNA pull-down assays followed by mass spectrometry and RNA immunoprecipitation analysis revealed that mechanistically HOXC13-AS sequestered the coat complex subunit alpha (COPA) protein and interfered wi...