Long Non-coding RNAs in Response to Genotoxic Stress
Long Non-coding RNAs in Response to Genotoxic Stress
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Abstract: Long non-coding RNAs(lncRNAs) are increasingly involved in diverse biological processes. Upon DNA damage, the DNA damage response(DDR) elicits a complex signaling cascade, which includes the induction of lncRNAs. LncRNA-mediated DDR is involved in non-canonical and canonical manners. DNA-damage induced lncRNAs contribute to the regulation of cell cycle, apoptosis, and DNA repair, thereby playing a key role in maintaining genome stability. This review summarizes the emerging role of lncRNAs in DNA damage and repair.
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Key words:
- Gene expression /
- Long non-coding RNA /
- DNA damage response /
- Regulatory mechanisms
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Figure 1. Model demonstrating the proposed mechanisms of lncRNA-mediated regulation of the p53 pathway, which controls cell cycle arrest, repair, and apoptosis in response to DNA damage. In response to DNA damage, p53 is stabilized and activated via phosphorylation mediated by the ATM/ATR pathway. p53 directly binds the target genes and regulates their expression to control cell cycle arrest, repair, and apoptosis. p21 and lincRNA-p21, which are transcribed near the p21 gene, are p53-target genes. LincRNA-p21 controls the expression of some p53-target genes. p53 function is partially mediated by gene regulation via lincRNA-p21.
Figure 2. Model demonstrating the proposed mechanisms of lncRNAs-mediated regulation of cyclin D1 and CDK6 induced by DNA damage. DNA damage induces the transcription of ncRNACCND1 from the promoter region of the cyclin D1 gene. NcRNACCND1 associates with and recruits TLS, an RNA-binding protein, to the cyclin D1 promoter, thereby preventing cyclin D1 gene transcription. DNA damage induces the expression of the lncRNAs, gadd7, which dissociates TDP-43 from the CDK6 mRNA to destabilize it, thereby downregulating CDK6 and inhibiting the G1/S transition.
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