The RNA-binding protein YBX1 regulates epidermal progenitors at a posttranscriptional level

• Published in: Nature communications 2018-04, Vol.9 (1), p.1734-16, Article 1734
• Main Authors: Kwon, Eunjeong, Todorova, Kristina, Wang, Jun, Horos, Rastislav, Lee, Kevin K., Neel, Victor A., Negri, Gian Luca, Sorensen, Poul H., Lee, Sam W., Hentze, Matthias W., Mandinova, Anna
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/109; 13/21; 13/89; 13/95; 3' Untranslated Regions; 38; 38/35; 38/39; 38/5; 38/77; 38/89; 38/91; 631/1647/767/2202; 631/337/572; 631/80/509; Animals; Cell Cycle - genetics; Cell Differentiation; Cell Proliferation; Cells (biology); Cellular Senescence; Chemokine CXCL1 - genetics; Chemokine CXCL1 - metabolism; Embryo, Mammalian; Epidermal Cells; Epidermis; Epidermis - growth & development; Epidermis - metabolism; Homeostasis; Humanities and Social Sciences; Humans; Interleukin-8 - genetics; Interleukin-8 - metabolism; Keratinocytes - cytology; Keratinocytes - metabolism; Mice; multidisciplinary; Post-transcription; Primary Cell Culture; Progenitor cells; Protein Binding; Proteins; Proteomes; Ribonucleic acid; RNA; RNA Processing, Post-Transcriptional; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA-binding protein; Science; Science (multidisciplinary); Senescence; Skin; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism; Y-Box-Binding Protein 1 - antagonists & inhibitors; Y-Box-Binding Protein 1 - genetics; Y-Box-Binding Protein 1 - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04092-0

The integrity of stratified epithelia depends on the ability of progenitor cells to maintain a balance between proliferation and differentiation. While much is known about the transcriptional pathways underlying progenitor cells’ behavior in the epidermis, the role of posttranscriptional regulation by mRNA binding proteins—a rate-limiting step in sculpting the proteome—remains poorly understood. Here we report that the RNA binding protein YBX1 (Y-box binding protein-1) is a critical effector of progenitors’ function in the epidermis. YBX1 expression is restricted to the cycling keratinocyte progenitors in vivo and its genetic ablation leads to defects in the architecture of the skin. We further demonstrate that YBX1 negatively controls epidermal progenitor senescence by regulating the translation of a senescence-associated subset of cytokine mRNAs via their 3′ untranslated regions. Our study establishes YBX1 as a posttranscriptional effector required for maintenance of epidermal homeostasis. The integrity of the stratified epithelia relies on controlled cell turnover but it is unclear how mRNA binding proteins regulates this. Here, the authors show that the RNA binding protein Y-box binding protein-1 translationally represses cytokines, so preventing senescence and maintaining epidermal homeostasis.