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
Summary
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.
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