ArticleNucleic acids research2022
A loosened gating mechanism of RIG-I leads to autoimmune disorders.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Interferon-λ drives renal fibrosis by coordinating epithelial-fibroblast crosstalk.The Journal of experimental medicine · 2026Article
- Human RIG-I Antiviral Deficiency Caused by a Dominant-Negative Variant Locked in a Signaling-Inactive State.medRxiv : the preprint server for health sciences · 2026Article
- Review
- Immunoengineering of a Photocaged 5´-triphosphate Oligoribonucleotide Ligand for Spatiotemporal Control of RIG-I Activation in Cancer.Angewandte Chemie (International ed. in English) · 2025Article
- Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024Review
- Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors.International journal of molecular sciences · 2024Review
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- The molecular language of RNA 5' ends: guardians of RNA identity and immunity.RNA (New York, N.Y.) · 2024Review
- Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus.Nature communications · 2024Article
- The mCancers · 2023Article
- Mechanobiology research in China.Mechanobiology in medicine · 2023Review
- Activation of cytosolic RNA sensors by endogenous ligands: roles in disease pathogenesis.Frontiers in immunology · 2023Review
- DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome.Frontiers in immunology · 2023Article
- Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DDX58 encodes RIG-I, a cytosolic RNA sensor that ensures immune surveillance of nonself RNAs. Individuals with RIG-IE510V and RIG-IQ517H mutations have increased susceptibility to Singleton-Merten syndrome (SMS) defects, resulting in tissue-specific (mild) and classic (severe) phenotypes. The coupling between RNA recognition and conformational changes is central to RIG-I RNA proofreading, but the molecular determinants leading to dissociated disease phenotypes remain unknown. Herein, we employed hydrogen/deuterium exchange mass spectrometry (HDX-MS) and single molecule magnetic tweezers (MT) to precisely examine how subtle conformational changes in the helicase insertion domain (HEL2i) promote impaired ATPase and erroneous RNA proofreading activities. We showed that the mutations cause a loosened latch-gate engagement in apo RIG-I, which in turn gradually dampens its self RNA (Cap2 moiety:m7G cap and N1-2-2'-O-methylation RNA) proofreading ability, leading to increased immunopathy. These results reveal HEL2i as a unique checkpoint directing two specialized functions, i.e. stabilizing the CARD2-HEL2i interface and gating the helicase from incoming self RNAs; thus, these findings add new insights into the role of HEL2i in the control of antiviral innate immunity and autoimmunity diseases.
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Registered trials
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.