Evidence map›Paper›PMID 42282823›Full record

ArticlebioRxiv : the preprint server for biology2026

Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.

Jie Chen, ZongChao Mo, Sixing Chen, Xi Wang, Tiffany Hsu, Celia Torres, Kathy Fange Liu, Sun Hur, Qin Li, Roger A Greenberg

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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

10 authors.

Jie ChenDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
ZongChao MoDepartment of Genetics, Penn Center for Genome Integrity, Penn Institute for Immunology & Immune Health (I3H), Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Sixing ChenDepartment of Genetics, University of Pennsylvania; Philadelphia, PA 19104, USA.
Xi WangHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital; Boston, MA 02115, USA.
Tiffany HsuHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital; Boston, MA 02115, USA.ORCID 0000-0003-1041-8040
Celia TorresHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital; Boston, MA 02115, USA.
Kathy Fange LiuDepartment of Biochemistry and Biophysics, Penn Center for Genome Integrity, Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0001-5943-3888
Sun HurHoward Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children's Hospital; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School; Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital; Boston, MA 02115, USA.
Qin LiDepartment of Genetics, Penn Center for Genome Integrity, Penn Institute for Immunology & Immune Health (I3H), Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
Roger A GreenbergDepartment of Cancer Biology, Penn Center for Genome Integrity, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.ORCID 0000-0003-1326-8981

Funding

Tumor cell instrinsic DNA damage signaling to the immune responseP01CA265794 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Roger A Greenberg · 2023 to 2026
$8.5M
Roles of Chromatin Modification in BRCA1 Dependent DNA RepairR01CA174904 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Roger A Greenberg · 2013 to 2026
$4.8M
Beta cell death in early type 1 diabetes caused by innate immune response to inefficient RNA editingU01DK143477 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2025 to 2025
$1.8M
Elucidating the Mechanisms and Roles of RNA Editing and SensingR35GM162298 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Qin Li · 2026 to 2026
$447k
NCI NIH HHS P01 CA265794NCI NIH HHS R01 CA174904NIDDK NIH HHS U01 DK143477NIGMS NIH HHS R35 GM162298
6 · The paper itself

Abstract

ADAR1 converts adenosine to inosine in endogenous double-stranded RNAs (dsRNAs) to prevent excessive MDA5-driven interferon-stimulated gene expression. The source of endogenous immunogenic dsRNAs remains enigmatic because only a small fraction of ADAR1 substrates activate MDA5, and cellular MDA5 filaments have not been isolated. Here, we couple affinity purification of cellular MDA5 filaments with RNA sequencing to define immunogenic endogenous dsRNAs. Greater than 84% of dsRNAs suppressed by combined DDX3X RNA helicase and ADAR1 base-editing activities were present in MDA5 filaments, compared to less than 1% of dsRNA substrates acted on by ADAR1 alone. Dual substrate dsRNAs consisted of inverted repeats embedded in 3'-UTRs with high base-pair complementarity and longer intervening sequences between repeats, with a minor contribution coming from intermolecular dsRNAs formed by sense and antisense transcripts. Moreover, the majority of dual substrate immunogenic dsRNAs were hyperedited in DDX3X mutant cancers. This reveals the identity of endogenous immunogenic dsRNAs and quality control mechanisms underlying their suppression.

Identifiers

PMID42282823
PMCPMC13251931

What OpenQuestion holds

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Registered trials

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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.