Abstract

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.

Details

Title
The RNA-binding protein YBX1 regulates epidermal progenitors at a posttranscriptional level
Author
Kwon, Eunjeong 1 ; Todorova, Kristina 1 ; Wang, Jun 1 ; Horos, Rastislav 2 ; Lee, Kevin K 1 ; Neel, Victor A 3 ; Negri, Gian Luca 4 ; Sorensen, Poul H 4 ; Lee, Sam W 5 ; Hentze, Matthias W 2 ; Mandinova, Anna 6 

 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA 
 European Molecular Biology Laboratory (EMBL), Heidelberg, Germany 
 Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA 
 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada 
 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA 
 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA 
Pages
1-16
Publication year
2018
Publication date
Apr 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2032750505
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.