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The modulation of AUF1 regulates the R-loop resolution activating the immune response in DDR

Maria Carmen Ragosta1, Alessandro di Vaio2, Maria Cuomo2

  • 1Scuola Superiore Meridionale (SSM, School of Advanced Studies), Clinical and Translational Oncology Program, University of Naples Federico II, Naples, Italy.

Iscience
|May 25, 2026
PubMed

Insights

AUF1 protein deregulation causes R-loop accumulation and export to the cytoplasm after DNA damage. This activates innate immune signaling, linking DNA repair defects to potential cancer therapies.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cancer Research

Background:

  • The DNA damage response (DDR) is crucial for maintaining genomic stability.
  • R-loops, DNA-RNA hybrids, can be exported to the cytoplasm after DNA damage, potentially activating immune responses.
  • AUF1 (AU-rich element RNA-binding protein 1) is implicated in RNA processing and has been linked to homologous recombination repair.

Purpose of the Study:

  • To investigate the role of AUF1 in DNA repair and immune activation following DNA damage.
  • To explore the link between AUF1 deregulation, R-loop dynamics, and the cGAS-STING innate immune pathway.

Main Methods:

  • Cellular assays to assess DNA damage response pathways.
  • Analysis of R-loop formation and localization.
  • Investigation of the cGAS-STING signaling pathway activation.

Main Results:

  • AUF1 deregulation leads to the accumulation and cytoplasmic export of R-loops after DNA damage.
  • Exported R-loops activate the cGAS-STING signaling pathway, indicating an innate immune response.
  • These findings establish a connection between defective DNA repair and innate immunity.

Conclusions:

  • AUF1 plays a critical role in regulating R-loop homeostasis and preventing aberrant immune activation.
  • Deregulation of AUF1 links impaired genome stability to innate immune signaling, offering potential therapeutic strategies for cancer.
Keywords:
ImmunologyMolecular biology

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