ArticleNature communications2021
Reciprocal regulation of RIG-I and XRCC4 connects DNA repair with RIG-I immune signaling.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Loss of JAK1 Function Causes G2-M Cell-Cycle Defects Vulnerable to KIF18A Inhibition.Cancer research · 2026Article
- USP39 promotes antiviral defense through post-transcriptional control of RIG-I and stabilization of STING.PLoS biology · 2026Article
- Article
- Multi-omics analysis reveals the role of the XRCC gene family in diagnosis, prognosis, and immunity in pan-cancer.Discover oncology · 2026Article
- The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025Review
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Systemic administration of an RNA binding and cell-penetrating antibody targets therapeutic RNA to multiple mouse models of cancer.Science translational medicine · 2025Article
- RIG-I-driven CDKN1A stabilization reinforces cellular senescence.Science China. Life sciences · 2025Article
- Review
- Article
- SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.Oncogenesis · 2024Article
- ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR-dependent transcription.Theranostics · 2024Article
- ATG7/GAPLINC/IRF3 axis plays a critical role in regulating pathogenesis of influenza A virus.PLoS pathogens · 2024Article
- MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC.Cell & bioscience · 2023Article
- X-ray cross-complementing family: the bridge linking DNA damage repair and cancer.Journal of translational medicine · 2023Review
- Article
- Review
- RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.International journal of molecular sciences · 2023Article
- Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer.BMC bioinformatics · 2023Article
- Exploiting RIG-I-like receptor pathway for cancer immunotherapy.Journal of hematology & oncology · 2023Review
Corrections and comments
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
The RNA-sensing pathway contributes to type I interferon (IFN) production induced by DNA damaging agents. However, the potential involvement of RNA sensors in DNA repair is unknown. Here, we found that retinoic acid-inducible gene I (RIG-I), a key cytosolic RNA sensor that recognizes RNA virus and initiates the MAVS-IRF3-type I IFN signaling cascade, is recruited to double-stranded breaks (DSBs) and suppresses non-homologous end joining (NHEJ). Mechanistically, RIG-I interacts with XRCC4, and the RIG-I/XRCC4 interaction impedes the formation of XRCC4/LIG4/XLF complex at DSBs. High expression of RIG-I compromises DNA repair and sensitizes cancer cells to irradiation treatment. In contrast, depletion of RIG-I renders cells resistant to irradiation in vitro and in vivo. In addition, this mechanism suggests a protective role of RIG-I in hindering retrovirus integration into the host genome by suppressing the NHEJ pathway. Reciprocally, XRCC4, while suppressed for its DNA repair function, has a critical role in RIG-I immune signaling through RIG-I interaction. XRCC4 promotes RIG-I signaling by enhancing oligomerization and ubiquitination of RIG-I, thereby suppressing RNA virus replication in host cells. In vivo, silencing XRCC4 in mouse lung promotes influenza virus replication in mice and these mice display faster body weight loss, poorer survival, and a greater degree of lung injury caused by influenza virus infection. This reciprocal regulation of RIG-I and XRCC4 reveals a new function of RIG-I in suppressing DNA repair and virus integration into the host genome, and meanwhile endues XRCC4 with a crucial role in potentiating innate immune response, thereby helping host to prevail in the battle against virus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.