HNRNPK maintains epidermal progenitor function through transcription of proliferation genes and degrading differentiation promoting mRNAs

Jingting Li, Yifang Chen, Xiaojun Xu, Jackson Jones, Manisha Tiwari, Ji Ling, Ying Wang, Olivier Harismendy and George L. Sen ()
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Jingting Li: University of California, San Diego
Yifang Chen: University of California, San Diego
Xiaojun Xu: University of California, San Diego
Jackson Jones: University of California, San Diego
Manisha Tiwari: University of California, San Diego
Ji Ling: University of California, San Diego
Ying Wang: University of California, San Diego
Olivier Harismendy: University of California, San Diego
George L. Sen: University of California, San Diego

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Maintenance of high-turnover tissues such as the epidermis requires a balance between stem cell proliferation and differentiation. The molecular mechanisms governing this process are an area of investigation. Here we show that HNRNPK, a multifunctional protein, is necessary to prevent premature differentiation and sustains the proliferative capacity of epidermal stem and progenitor cells. To prevent premature differentiation of progenitor cells, HNRNPK is necessary for DDX6 to bind a subset of mRNAs that code for transcription factors that promote differentiation. Upon binding, these mRNAs such as GRHL3, KLF4, and ZNF750 are degraded through the mRNA degradation pathway, which prevents premature differentiation. To sustain the proliferative capacity of the epidermis, HNRNPK is necessary for RNA Polymerase II binding to proliferation/self-renewal genes such as MYC, CYR61, FGFBP1, EGFR, and cyclins to promote their expression. Our study establishes a prominent role for HNRNPK in maintaining adult tissue self-renewal through both transcriptional and post-transcriptional mechanisms.

Date: 2019
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DOI: 10.1038/s41467-019-12238-x

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