Evidence map›Paper›PMID 40229436›Full record

ArticleNature cell biology2025

Targeting a key disulfide linkage to regulate RIG-I condensation and cytosolic RNA-sensing.

Bin Wang, Yongqiang Wang, Ting Pan, Lili Zhou, Yu Ran, Jing Zou, Xiaohua Yan, Zhenke Wen, Shixian Lin, Aiming Ren and 7 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Nonsense-mediated decay controls a negative feedback loop in innate immune sensing.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Bin Wang *Department of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Yongqiang Wang *Institutes of Biology and Medical Sciences, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, China.
Ting Pan *Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases, School of Medicine, Sun Yat-sen University, Shenzhen, China.ORCID http://orcid.org/0000-0002-7106-7312
Lili ZhouInstitutes of Biology and Medical Sciences, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, China.
Yu RanDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Jing ZouDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Xiaohua YanThe MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, The First Affiliated Hospital, Jiangxi Medical College Nanchang University, Nanchang, China.
Zhenke WenInstitutes of Biology and Medical Sciences, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, China.
Shixian LinDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0001-9718-9986
Aiming RenDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.
Fangwei WangDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0001-5617-282X
Zhuang LiuJiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, China.
Ting LiuDepartments of Cell Biology and General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0002-7956-3396
Huasong LuDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China.ORCID http://orcid.org/0000-0003-0875-5531
Bing YangDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China. bingyang@zju.edu.cn.ORCID http://orcid.org/0000-0001-6739-2932
Fangfang ZhouInstitutes of Biology and Medical Sciences, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, China. zhoufangfang@suda.edu.cn.ORCID http://orcid.org/0000-0003-1870-7584
Long ZhangDepartment of Radiation Oncology and the State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University, Hangzhou, China. L_Zhang@zju.edu.cn.ORCID http://orcid.org/0000-0001-8139-0474

Funding

Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation) 19KJA550003
6 · The paper itself

Abstract

Maintaining innate immune homeostasis is critical for preventing infections and autoimmune diseases but effective interventions are lacking. Here we identified C864-C869-mediated intermolecular disulfide-linkage formation as a critical step for human RIG-I activation that can be bidirectionally regulated to control innate immune homeostasis. The viral-stimulated C864-C869 disulfide linkage mediates conjugation of an SDS-resistant RIG-I oligomer, which prevents RIG-I degradation by E3 ubiquitin-ligase MIB2 and is necessary for RIG-I to perform liquid-liquid phase separation to compartmentalize downstream signalsome, thereby stimulating type I interferon signalling. The corresponding C865S 'knock-in' caused an oligomerization defect and liquid-liquid phase separation in mouse RIG-I, which inhibited innate immunity, resulting in increased viral load and mortality in mice. Using unnatural amino acids to generate covalent C864-C869 linkage and the development of an interfering peptide to block C864-C869 residues, we bidirectionally regulated RIG-I activities in human diseases. These findings provide in-depth insights on mechanism of RIG-I activation, allowing for the development of methodologies that hold promising implications in clinics.

Indexed as

CytosolDEAD Box Protein 58DisulfidesImmunity, InnateAnimalsHEK293 CellsHumansInterferon Type IMiceMice, Inbred C57BLProtein MultimerizationReceptors, ImmunologicSignal TransductionUbiquitin-Protein LigasesDdx58 protein, mouseDEAD Box Protein 58DisulfidesInterferon Type IReceptors, ImmunologicRIGI protein, humanUbiquitin-Protein Ligases

Identifiers

What OpenQuestion holds

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Registered trials

None linked

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.