PIWIL-2 and piRNAs are regularly expressed in epithelia of the skin and their expression is related to differentiation

Johannes Pammer,Leopold Eckhart,Maria Buchberger,Laura Monschein,Martin Bilban,Michael Mildner,Heidi Rossiter

doi:10.1007/s00403-020-02052-7

Johannes Pammer, Leopold Eckhart + Show 5 more

Open Access

https://doi.org/10.1007/s00403-020-02052-7

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Abstract

PIWI proteins play multiple roles in germline stem cell maintenance and self-renewal. PIWI-interacting RNAs (piRNAs) associate with PIWI proteins, form effector complexes and maintain genome integrity and function in the regulation of gene expression by epigenetic modifications. Both are involved in cancer development. In this study, we investigated the expression of PIWIL-2 and piRNAs in normal human skin and epithelial tumors and its regulation during keratinocyte (KC) differentiation. Immunohistochemistry showed that PIWIL-2 was regularly expressed in the epidermis and adnexal tissue with strongest expression in sebaceous glands. Cell culture studies revealed an association of PIWIL-2 expression with the state of differentiated KC. In contrast, the PIWIL-2 expression pattern did not correlate with stem cell compartments or malignancy. piRNAs were consistently detected in KC in vitro by next-generation sequencing and the expression levels of numerous piRNAs were regulated during KC differentiation. Epidermal piRNAs were predominantly derived from processed snoRNAs (C/D-box snoRNAs), tRNAs and protein coding genes. Our data indicate that components of the PIWIL-2—piRNA pathway are present in epithelial cells of the skin and are regulated in the context of KC differentiation, suggesting a role of somatic gene regulation. However, putative roles in the maintenance of stem cell compartments or the development of malignancy in the skin were not supported by this study.

Highlights

The skin is the largest barrier against various physical, chemical or biological stresses, constituting the first line of defense of the body
When comparing the sequence of 100 PIWI-interacting RNAs (piRNAs) with the strongest expression level to non-coding RNAs, we found 39 of them to be homologous to tRNAs, 27 to Small nucleolar RNAs (snoRNAs) (SNORDs, mostly C/D-box snoRNAs) and 5 to miRNAs (Supplementary information, Table 3)
We describe that PIWIL-2 is regularly expressed in epidermal KC, epithelial cells of skin appendages as well as in mesenchymal cells

Summary

Introduction

The skin is the largest barrier against various physical, chemical or biological stresses, constituting the first line of defense of the body. This function is dependent on both epidermal and skin adnexal differentiation and maintenance [12]. Whereas the role of gene expression and regulation. Small non-coding RNAs regulate gene expression by binding to AGO and PIWI proteins. AGO proteins have been shown to connect to miRNAs and small interfering RNAs (siRNA) and to regulate translation, mRNA degradation and heterochromatin formation. PIWI proteins bind to piRNAs with a length of ~ 26–31 nucleotides [21]

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