<p>Cytoplasmic DNA-RNA hybrids are emerging as important immunogenic nucleic acids, that were previously underappreciated. DNA-RNA hybrids, formed during cellular processes like transcription and replication, or by exogenous pathogens, are recognized by pattern recognition receptors (PRRs), including cGAS, DDX41, and TLR9, which trigger immune responses. Post-translational modifications (PTMs) including ubiquitination, phosphorylation, acetylation, and palmitoylation regulate the activity of PRRs and downstream signaling molecules, fine-tuning the immune response. Targeting enzymes involved in DNA-RNA hybrid metabolism and PTMs regulation offers therapeutic potential for inflammatory diseases. Herein, we discuss the sources, immune response, and therapeutic implications of DNA-RNA hybrids in inflammation, highlighting the significance of DNA-RNA hybrids as potential targets for the treatment of inflammation.</p>

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DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications

  • Litao Chen,
  • Lechen Hu,
  • Han Chang,
  • Jianing Mao,
  • Meng Ye,
  • Xiaofeng Jin

摘要

Cytoplasmic DNA-RNA hybrids are emerging as important immunogenic nucleic acids, that were previously underappreciated. DNA-RNA hybrids, formed during cellular processes like transcription and replication, or by exogenous pathogens, are recognized by pattern recognition receptors (PRRs), including cGAS, DDX41, and TLR9, which trigger immune responses. Post-translational modifications (PTMs) including ubiquitination, phosphorylation, acetylation, and palmitoylation regulate the activity of PRRs and downstream signaling molecules, fine-tuning the immune response. Targeting enzymes involved in DNA-RNA hybrid metabolism and PTMs regulation offers therapeutic potential for inflammatory diseases. Herein, we discuss the sources, immune response, and therapeutic implications of DNA-RNA hybrids in inflammation, highlighting the significance of DNA-RNA hybrids as potential targets for the treatment of inflammation.