Abstract

A wide variety of biological effects are induced in cells that are exposed to ionizing radiation. The expression changes of coding mRNA and non-coding micro-RNA have been implicated in irradiated cells. The involvement of other classes of non-coding RNAs (ncRNA), such as small nucleolar RNAs (snoRNAs), long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs) in cells recovering from radiation-induced damage has not been examined. Thus, we investigated whether these ncRNA were undergoing changes in cells exposed to ionizing radiation. The modulation of ncRNAs expression was determined in human TK6 (p53 positive) and WTK1 (p53 negative) cells. The snoRNA host genes SNHG1, SNHG6, and SNHG11 were induced in TK6 cells. In WTK1 cells, SNHG1 was induced but SNHG6, and SNHG11 were repressed. SNHG7 was repressed in TK6 cells and was upregulated in WTK1 cells. The lncRNA MALAT1 and SOX2OT were induced in both TK6 and WTK1 cells and SRA1 was induced in TK6 cells only. Interestingly, the MIAT and PIWIL1 were not expressed in TK6 cells before or after the ionizing radiation treatment. The MIAT and PIWIL1 were upregulated in WTK1 cells. This data provides evidence that altered ncRNA expression is a part of the complex stress response operating in radiation-treated cells and this response depends on functional p53.

Highlights

  • The cellular response to ionizing radiation (IR) damage is complex and relies on simultaneous activation of a number of signaling networks

  • If so, are there differences or similarities in the non-coding RNAs (ncRNA) responses in cells that are sensitive or resistant to radiation-induced killing? We focused on small nucleolar RNAs host genes, long ncRNAs, and PIWI-interacting RNAs after radiation exposure of human cells

  • WTK1 cells as compared to TK6 cells indicating dissimilar functions in the IR- induced stress response operating in these cells

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Summary

Introduction

The cellular response to ionizing radiation (IR) damage is complex and relies on simultaneous activation of a number of signaling networks. We and other research groups have published the modulation of miRNA in radiation-treated human cells [10,11]. Later studies from our laboratory examined the impact of radiation dose, dose rate, cellular sensitivity to radiation, and DNA repair capability of the cell on the modulation of miRNA in irradiated human cells [12,13,14,15]. We asked whether other non-coding RNAs (ncRNAs) beside miRNA are modulated in irradiated cells. We focused on small nucleolar RNAs (snoRNAs) host genes, long ncRNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs) after radiation exposure of human cells. The snoRNAs are a subset of ncRNA with a wide variety of cellular functions, such as chemical modification of RNA, pre-RNA processing and control of alternative splicing [16]. A novel class of small RNAs, called PIWI-interacting RNAs (piRNAs), maintains genome integrity by epigenetically silencing transposons via DNA methylation [20]. piRNAs interact exclusively with the PIWI family of proteins

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