2. Academic Validation
  3. HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury

HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury

  • Clin Transl Med. 2023 Jul;13(7):e1336. doi: 10.1002/ctm2.1336.
Yi-Qian Feng 1,  Heng Zhang 1 2,  Jing-Xia Han 1 2,  Bi-Jia Cui 1,  Lu-Ning Qin 1,  Lei Zhang 1,  Qing-Qing Li 1,  Xin-Ying Wu 1,  Nan-Nan Xiao 1,  Yan Zhang 1,  Ting-Ting Lin 3,  Hui-Juan Liu 1 2,  Tao Sun 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • 2 Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
  • 3 Medical Plastic and Cosmetic Centre, Tianjin Branch of National Clinical Research Center for Ocular Disease, Tianjin Medical University Eye Hospital, Tianjin, China.
PMID: 37461263 DOI: 10.1002/ctm2.1336
Abstract

Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited.

Keywords

DNA damage; R-loop; UV irradiation; small-molecule drugs; transcription factor regulation.

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