ArticleCell reports2021
TDP-43 prevents endogenous RNAs from triggering a lethal RIG-I-dependent interferon response.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- LncRNAs LCETRL3 and LCETRL4 at chromosome 4q12 diminish EGFR-TKIs efficiency in NSCLC through stabilizing TDP43 and EIF2S1.Signal transduction and targeted therapy · 2022Trial
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- YBX1 regulates RNA polymerase III transcripts to prevent inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- TYK2 mediates neuroinflammation in Alzheimer's disease brains with TDP-43 pathology.Nature communications · 2026Article
- RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodegeneration and Offers New Biomarker-Driven Individualized Treatment Options for (FUS-)ALS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TDP-43 dysfunction leads to the accumulation of cryptic transposable element-derived exons, crypTEs, in iPSC derived neurons and ALS/FTD patient tissues.bioRxiv : the preprint server for biology · 2026Article
- An autoinflammatory RIG-I variant causing Singleton-Merten syndrome associates with small non-coding Y-RNAs.Discovery immunology · 2026Article
- Dysregulated programmed cell death of intestinal epithelial cells in ulcerative colitis: Molecular mechanisms and novel therapeutic interventions (Review).International journal of molecular medicine · 2025Review
- Interferon-induced protein ISG15 in the central nervous system, quo vadis?FEBS letters · 2025Review
- TDP-43: unveiling the hidden key to cellular fate decisions.Cell communication and signaling : CCS · 2025Review
- Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease.Nature reviews. Molecular cell biology · 2025Review
- The differential impact of HNRNPA1 isoforms on gene expression and their relevance to dsRNA-mediated innate immune response.Scientific reports · 2025Article
- Proteomics Analysis of the TDP-43 Interactome in Cellular Models of ALS Pathogenesis.Journal of neurochemistry · 2025Article
- Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator.Nature communications · 2025Article
- scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy.PloS one · 2025Article
- Recent Advances of Type I Interferon on the Regulation of Immune Cells and the Treatment of Systemic Lupus Erythematosus.Journal of inflammation research · 2025Review
- Article
- The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
RIG-I-like receptors (RLRs) are involved in the discrimination of self versus non-self via the recognition of double-stranded RNA (dsRNA). Emerging evidence suggests that immunostimulatory dsRNAs are ubiquitously expressed but are disrupted or sequestered by cellular RNA binding proteins (RBPs). TDP-43 is an RBP associated with multiple neurological disorders and is essential for cell viability. Here, we demonstrate that TDP-43 regulates the accumulation of immunostimulatory dsRNA. The immunostimulatory RNA is identified as RNA polymerase III transcripts, including 7SL and Alu retrotransposons, and we demonstrate that the RNA-binding activity of TDP-43 is required to prevent immune stimulation. The dsRNAs activate a RIG-I-dependent interferon (IFN) response, which promotes necroptosis. Genetic inactivation of the RLR-pathway rescues the interferon-mediated cell death associated with loss of TDP-43. Collectively, our study describes a role for TDP-43 in preventing the accumulation of endogenous immunostimulatory dsRNAs and uncovers an intricate relationship between the control of cellular gene expression and IFN-mediated cell death.
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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.