ArticlePLoS pathogens2013
A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 198 citations in OpenAlex.
- DZIP3 is a viral RNA co-sensor for RIG-I that promotes type-I interferon responses.The EMBO journal · 2026Article
- Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.Biochemical Society transactions · 2026Review
- The segmented flavivirus ALSV-encoded nucleoprotein VP2 inhibits type I interferon production by targeting RIG-I.Microbiology spectrum · 2026Article
- Article
- Structure, Function and Inhibition of Helicases Involved in Virus Infection.Biomolecules · 2026Review
- Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy.The FEBS journal · 2026Review
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- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- From viruses to cancer: exploring the role of the hepatitis C virus NS3 protein in carcinogenesis.Infectious agents and cancer · 2024Review
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- Host Factors Modulate Virus-Induced IFN Production via Pattern Recognition Receptors.Journal of inflammation research · 2024Review
- Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host's Immunity.International journal of molecular sciences · 2023Review
- Antiviral Activity of Zinc Finger Antiviral Protein (ZAP) in Different Virus Families.Pathogens (Basel, Switzerland) · 2023Review
- Suppression of Innate Immunity by the Hepatitis C Virus (HCV): Revisiting the Specificity of Host-Virus Interactive Pathways.International journal of molecular sciences · 2023Review
- Viral evasion of the interferon response at a glance.Journal of cell science · 2023Review
- ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62.Virology journal · 2023Article
- Crosstalk between Autophagy and RLR Signaling.Cells · 2023Review
- TheProceedings of the National Academy of Sciences of the United States of America · 2023Article
- K63-linked polyubiquitination of LGP2 by Riplet regulates RIG-I-dependent innate immune response.EMBO reports · 2023Article
- Cytokine Receptor-Like Factor 3 Negatively Regulates Antiviral Immunity by Promoting the Degradation of TBK1 in Teleost Fish.Journal of virology · 2023Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The innate immune system is essential for controlling viral infections, but several viruses have evolved strategies to escape innate immunity. RIG-I is a cytoplasmic viral RNA sensor that triggers the signal to induce type I interferon production in response to viral infection. RIG-I activation is regulated by the K63-linked polyubiquitin chain mediated by Riplet and TRIM25 ubiquitin ligases. TRIM25 is required for RIG-I oligomerization and interaction with the IPS-1 adaptor molecule. A knockout study revealed that Riplet was essential for RIG-I activation. However the molecular mechanism underlying RIG-I activation by Riplet remains unclear, and the functional differences between Riplet and TRIM25 are also unknown. A genetic study and a pull-down assay indicated that Riplet was dispensable for RIG-I RNA binding activity but required for TRIM25 to activate RIG-I. Mutational analysis demonstrated that Lys-788 within the RIG-I repressor domain was critical for Riplet-mediated K63-linked polyubiquitination and that Riplet was required for the release of RIG-I autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling. We investigated the biological importance of this mechanism in human cells and found that hepatitis C virus (HCV) abrogated this mechanism. Interestingly, HCV NS3-4A proteases targeted the Riplet protein and abrogated endogenous RIG-I polyubiquitination and association with TRIM25 and TBK1, emphasizing the biological importance of this mechanism in human antiviral innate immunity. In conclusion, our results establish that Riplet-mediated K63-linked polyubiquitination released RIG-I RD autorepression, which allowed the access of positive factors to the RIG-I protein.
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