Evidence map›Paper›PMID 42709850›Full record

ArticlePLoS pathogens2026

TRIM21 blocks DDX3X-driven stress granule formation during Mycobacterium tuberculosis infection via a non-canonical E3 ligase mechanism.

Ruiyao Xu, Mengru Lu, Gaoyan Wang, Ximeng Zhang, Yuxing Huang, Yu Wang, Qing Yu, Yaxuan Wang, Dan Chen, Yunlong Hu and 5 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Ruiyao XuGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.ORCID 0000-0002-3005-1728
Mengru LuGuangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Gaoyan WangGuangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Ximeng ZhangGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Yuxing HuangGuangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Yu WangGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Qing YuGuangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Yaxuan WangGuangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Dan ChenGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Yunlong HuGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Chenyan ShiGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Yi CaiGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Li FuGuangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Center, School of Medicine, Shenzhen, China.
Xinchun ChenGuangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, China.
Youchao DaiGuangzhou Medical Research Institute of Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

Funding

National Natural Science Foundation of ChinaScience and Technology Project of Guangdong ProvinceShenzhen Medical Research Fund
6 · The paper itself

Abstract

Tripartite motif-containing 21 (TRIM21) is an E3 ubiquitin ligase that binds viral and host proteins to mediate antiviral defense. Its role in Mycobacterium tuberculosis (Mtb) infection, however, is unclear. Here, our analysis of human TB transcriptomic datasets showed that TRIM21 expression levels correlate with TB progression in human patients. We further demonstrated that TRIM21 deficiency suppresses Mtb growth in both macrophages and a murine model of tuberculosis (TB). Mechanistically, TRIM21 limits host resistance to Mtb through a non-canonical pathway distinct with its E3 ligase activity. It physically interacts with the RNA helicase DEAD-box helicase family member DDX3X and disrupts phase separation dynamics required for stress granule (SG) assembly. Impaired SG formation compromises innate immune responses, thereby facilitating intracellular bacterial growth and creating a permissive cellular environment for Mtb growth. Consistent with these genetic findings, pharmacological inhibition of TRIM21 restricted Mtb growth in experimental macrophage and murine models. Together, these findings uncover a non-canonical role of TRIM21 in Mtb infection and highlight its potential as a therapeutic target for host-directed therapy against TB.

Indexed as

DEAD-box RNA HelicasesMycobacterium tuberculosisRibonucleoproteinsStress GranulesTuberculosisUbiquitin-Protein LigasesAnimalsHumansImmunity, InnateMacrophagesMiceSS-A AntigenTRIM21 ProteinDDX3X protein, humanDdx3x protein, mouseDEAD-box RNA HelicasesRibonucleoproteinsSS-A AntigenTRIM21 ProteinUbiquitin-Protein Ligases

Identifiers

PMID42709850
PMCPMC13552953

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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.