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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

m7G modification in mRNA cooperates with QKI to promote homologous recombination repair

  • Xinyun Chen1,2
  • Mengyan Li1
  • Zhichao Liu3
  • Longjiang Di1
  • Qingren Meng1
  • Tingting Feng1
  • Jun Zhang1
  • Qian Zhu1
  • Xiaopeng Lu1
  • Yuxin Shu1,4
  • Jinbo Huang1
  • Monika Gullerova3
2 more authors
  • Yuan Tian1
  • Wei-Guo Zhu1,4
4 affiliations
  1. 1International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen 518055, China
  2. 2Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
  3. 3Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
  4. 4Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wannan Medical College, Wuhu 241002, Anhui, China
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Abstract

DNA double strand breaks (DSBs) are repaired through distinct pathways, with homologous recombination (HR) favored when DNA ends undergo extensive resection. Although cytoplasmic N7-methylguanosine (m7G)-modified RNA increases after UV-induced single-strand breaks, its role in DSB repair (including HR) remains unclear. Here, we show that m7G-modified RNA accumulates at DSB sites, where it recruits the m7G reader protein Quaking (QKI)5, to selectively promote HR. Mechanistically, QKI5 directly interacts with MRE11 and enhances its DNA binding affinity, thereby facilitating DNA end resection. Depletion of QKI5 impairs recruitment of the MRE11–RAD50–NBS1 complex to DSBs and reduces HR repair efficiency. Moreover, elevated QKI5 expression is associated with resistance to radiotherapy in both mouse models and clinical cohorts. Together, these findings identify the m7G RNA–QKI5–MRE11 axis as a regulator of HR pathway choice and suggest QKI5 as a promising therapeutic target in cancer treatment.

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Cite

BibTeXRIS
BibTeX
@article{chen2026modification,
  title = {{m7G modification in mRNA cooperates with QKI to promote homologous recombination repair}},
  author = {Xinyun Chen and Mengyan Li and Zhichao Liu and Longjiang Di and Qingren Meng and Tingting Feng and Jun Zhang and Qian Zhu and Xiaopeng Lu and Yuxin Shu and Jinbo Huang and Monika Gullerova and Yuan Tian and Wei-Guo Zhu},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2611667123},
  url = {https://doi.org/10.1073/pnas.2611667123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - m7G modification in mRNA cooperates with QKI to promote homologous recombination repair
AU  - Xinyun Chen
AU  - Mengyan Li
AU  - Zhichao Liu
AU  - Longjiang Di
AU  - Qingren Meng
AU  - Tingting Feng
AU  - Jun Zhang
AU  - Qian Zhu
AU  - Xiaopeng Lu
AU  - Yuxin Shu
AU  - Jinbo Huang
AU  - Monika Gullerova
AU  - Yuan Tian
AU  - Wei-Guo Zhu
PY  - 2026
DA  - 2026/10/22
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2611667123
UR  - https://doi.org/10.1073/pnas.2611667123
AB  - DNA double strand breaks (DSBs) are repaired through distinct pathways, with homologous recombination (HR) favored when DNA ends undergo extensive resection. Although cytoplasmic N7-methylguanosine (m7G)-modified RNA increases after UV-induced single-strand breaks, its role in DSB repair (including HR) remains unclear. Here, we show that m7G-modified RNA accumulates at DSB sites, where it recruits the m7G reader protein Quaking (QKI)5, to selectively promote HR. Mechanistically, QKI5 directly interacts with MRE11 and enhances its DNA binding affinity, thereby facilitating DNA end resection. Depletion of QKI5 impairs recruitment of the MRE11–RAD50–NBS1 complex to DSBs and reduces HR repair efficiency. Moreover, elevated QKI5 expression is associated with resistance to radiotherapy in both mouse models and clinical cohorts. Together, these findings identify the m7G RNA–QKI5–MRE11 axis as a regulator of HR pathway choice and suggest QKI5 as a promising therapeutic target in cancer treatment.
SN  - 0027-8424
SN  - 1091-6490
ER  -