The RNA-binding protein YBX1 regulates epidermal progenitors at a posttranscriptional level
Eunjeong Kwon, Kristina Todorova, Jun Wang, Rastislav Horos, Kevin K. Lee, Victor A. Neel, Gian Luca Negri, Poul H. Sorensen, Sam W. Lee, Matthias W. Hentze, Anna Mandinova
Massachusetts General Hospital and Harvard Medical School, Charlestown
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.