2. Academic Validation
  3. The RNA-binding protein YBX1 regulates epidermal progenitors at a posttranscriptional level

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

  • Nat Commun. 2018 Apr 30;9(1):1734. doi: 10.1038/s41467-018-04092-0.
Eunjeong Kwon 1,  Kristina Todorova 1,  Jun Wang 1,  Rastislav Horos 2,  Kevin K Lee 1,  Victor A Neel 3,  Gian Luca Negri 4 5,  Poul H Sorensen 4 5,  Sam W Lee 1 6,  Matthias W Hentze 2,  Anna Mandinova 7 8 9
Affiliations

Affiliations

  • 1 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
  • 2 European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany.
  • 3 Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • 4 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V5Z 1L3, Canada.
  • 5 Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
  • 6 Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA, 02142, USA.
  • 7 Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. [email protected].
  • 8 Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA, 02142, USA. [email protected].
  • 9 Harvard Stem Cell Institute, 7 Divinity Avenue Cambridge, Cambridge, MA, 02138, USA. [email protected].
PMID: 29712925 DOI: 10.1038/s41467-018-04092-0
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.

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