RNF25 confers mRNA damage tolerance by curbing activation of the integrated stress response - PubMed
4 hours ago
- #chemotherapy
- #RNF25
- #RNA damage
- RNF25, a ubiquitin ligase, provides tolerance to RNA damage caused by the chemotherapeutic agent azacytidine.
- Azacytidine is incorporated into mRNA, causing lesions that stall ribosomes and activate the GCN2-dependent integrated stress response (ISR), leading to cell death.
- RNF25 prevents excessive ISR activation by ubiquitylating ribosomal protein eS31, thereby suppressing cell death during azacytidine treatment.
- This study identifies an mRNA damage tolerance mechanism that influences cellular survival in response to azacytidine, with implications for chemosensitivity in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).