Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
0numbers the graph read from it
0cells of the map it votes in
9citing 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.
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
16 authors.
Shuo RuDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0005-8198-528X
Sisi TangDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0002-4154-1754
Hui XuDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0000-6398-6178
Jiahao YinDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0005-9525-9211
Yan GuoDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0004-0750-6941
Liuping SongDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0009-2415-6791
Zhenyu JinDivision of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.ORCID 0000-0001-9464-2773
Danyel LeeSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0003-3124-0245
Yi-Hao ChanSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0003-0329-238X
Xingyao ChenDivision of Life Sciences and Medicine, Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, China.ORCID 0009-0008-8466-0642
Luke BuererDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.ORCID 0000-0003-1391-3370
William FairbrotherDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.ORCID 0000-0003-2694-4934
Weidong JiaDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0009-0008-1419-3401
Jean-Laurent CasanovaSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-7782-4169
Shen-Ying ZhangSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.ORCID 0000-0002-9449-3672
Daxing GaoDivision Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.ORCID 0000-0002-1493-4467
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6M
Study of the Cellular Basis of Herpes Simplex Encephalitis with hPSC-Derived CNS and PNS CellsR01NS072381 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova, Shen-Ying Zhang · 2010 to 2026
$10.2M
Monogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19R01AI088364 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova, Shen-Ying Zhang · 2010 to 2026
$8.7M
Chinese Academy of Sciences XDB0490000French Medical Research FoundationFrench National Research Agency ANR-10-LABX-62-IBEIDGeneral Atlantic FoundationHoward Hughes Medical InstituteImagine InstituteInstitut National de la Santé et de la Recherche MédicaleNational Key R&D Program of China 2023YFC2306100National Natural Science Foundation of China 31970855NCATS NIH HHS UL1 TR001866NIAID NIH HHS R01 AI088364NIH HHS R01AI088364NINDS NIH HHS R01 NS072381Paris Cité UniversityRockefeller UniversitySt. Giles FoundationUniversity of Science and Technology of China
6 · The paper itself
Abstract
The molecular mechanism by which inborn errors of the human RNA lariat-debranching enzyme 1 (DBR1) underlie brainstem viral encephalitis is unknown. We show here that the accumulation of RNA lariats in human DBR1-deficient cells interferes with stress granule (SG) assembly, promoting the proteasome degradation of at least G3BP1 and G3BP2, two key components of SGs. In turn, impaired assembly of SGs, which normally recruit PKR, impairs PKR activation and activity against viruses, including HSV-1. Remarkably, the genetic ablation of PKR abolishes the corresponding antiviral effect of DBR1 in vitro. We also show that Dbr1Y17H/Y17H mice are susceptible to similar viral infections in vivo. Moreover, cells and brain samples from Dbr1Y17H/Y17H mice exhibit decreased G3BP1/2 expression and PKR phosphorylation. Thus, the debranching of RNA lariats by DBR1 permits G3BP1/2- and SG assembly-mediated PKR activation and cell-intrinsic antiviral immunity in mice and humans. DBR1-deficient patients are prone to viral disease because of intracellular lariat accumulation, which impairs G3BP1/2- and SG assembly-dependent PKR activation.
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.
Human DBR1 deficiency impairs stress granule-dependent PKR antiviral immunity. · full record | OpenQuestion