A novel UVA ‐associated circUBE2I mediates ferroptosis in HaCaT cells

The canonical splicing ofUBE2I gene precursor mRNA (pre-mRNA) involves the removal of introns and joining of exons to create a mature messenger RNA (mRNA), which is translated into UBC9 protein. UVA irradiation in keratinocytes can induce the alternative back-splicing of theUBE2I gene generating a circular RNA, named circUBE2I, formed by exon 2 to exon 6. The circUBE2I is crucial in making skin cells more susceptible to ferroptosis, an iron-dependent form of regulated cell death, in response to UVA exposure or H2O2 treatment, by downregulating FTH1, GPX4, CD71, and xCT. AbstractAlternative splicing of precursor messenger RNA (pre-mRNA), including linear splicing and back splicing, produces multiple isoforms that lead to diverse cell fates in response to stimuli including ultraviolet radiation (UVR). Although UVR-induced linear gene splicing has been extensively studied in skin cells, the UVR-induced gene back-splicing events that lead to the production of circular RNAs (circRNAs) have not been thoroughly investigated. The present study used circRNA transcriptome sequencing to screen the differentially expressed circRNAs in human keratinocytes (HaCaT) after UVA irradiation. A total of 312 differentially expressed circRNAs were found in HaCaT cells post-UVR. Among the UVA-induced differentially expressed circRNAs, circUBE2I —a novel circRNA formed by exons 2–6 of the UBE2I gene—was the most significantly upregulated circRNA. RT–qPCR assay further confirmed the increase ...

Source: Photochemistry and Photobiology - November 21, 2023 Category: Science Authors: Peng Yi, Yan Huang, Xin Zhao, Zhengshan Qin, Danli Zhu, Li Liu, Yuxi Zheng, Jianguo Feng, Menghong Long Tags: RESEARCH ARTICLE Source Type: research