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Peer-reviewedCC BY-NC-NDProceedings of the National Academy of Sciences

MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS–STING activation

  • Zohirul Islam1
  • Ahsan Habib Polash2
  • Colin L. Sweeney3
  • Masataka Suzawa2
  • Bryan Chim1
  • Sabrina Sultana1
  • Skyler A. Kuhn4
  • Nicholas Cutrona1
  • 刘秀怀1
  • Patrick T Smith1
  • Tibor Z. Veres5
  • Juraj Kabát5
4 more authors
  • Sundar Ganesan5
  • Amir B. K. Foroushani1
  • Markus Hafner2
  • Stefan Adi Muljo1
5 affiliations
  1. 1Integrative Immunobiology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH
  2. 2RNA Molecular Biology Group, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH
  3. 3Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH
  4. 4Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
  5. 5Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH
Open at sourceDOICite

Abstract

Interferon-stimulated genes (ISGs) comprise a program of immune effectors important for host immune defense. When uncontrolled, ISGs play a central role in interferonopathies and other inflammatory diseases. The mechanisms responsible for turning on ISGs are not completely known. By investigating MATRIN3 (MATR3), a nuclear RNA-binding protein mutated in familial ALS, we found that perturbing MATR3 results in elevated expression of ISGs. Using an integrative approach, we elucidate a pathway that leads to activation of cGAS-STING. This outlines a plausible mechanism for pathogenesis in a subset of ALS, and suggests new diagnostic and therapeutic approaches for this fatal disease. One-Sentence Summary Mis-splicing of Tudor Domain Containing 3 ( TDRD3 ) in the absence of MATR3 unleashes R-loops and interferon-stimulated genes.

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Cite

BibTeXRIS
BibTeX
@article{islam2026matrin3,
  title = {{MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS–STING activation}},
  author = {Zohirul Islam and Ahsan Habib Polash and Colin L. Sweeney and Masataka Suzawa and Bryan Chim and Sabrina Sultana and Skyler A. Kuhn and Nicholas Cutrona and 刘秀怀 and Patrick T Smith and Tibor Z. Veres and Juraj Kabát and Sundar Ganesan and Amir B. K. Foroushani and Markus Hafner and Stefan Adi Muljo},
  journal = {Proceedings of the National Academy of Sciences},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2608835123},
  url = {https://doi.org/10.1073/pnas.2608835123},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS–STING activation
AU  - Zohirul Islam
AU  - Ahsan Habib Polash
AU  - Colin L. Sweeney
AU  - Masataka Suzawa
AU  - Bryan Chim
AU  - Sabrina Sultana
AU  - Skyler A. Kuhn
AU  - Nicholas Cutrona
AU  - 刘秀怀
AU  - Patrick T Smith
AU  - Tibor Z. Veres
AU  - Juraj Kabát
AU  - Sundar Ganesan
AU  - Amir B. K. Foroushani
AU  - Markus Hafner
AU  - Stefan Adi Muljo
PY  - 2026
DA  - 2026/10/07
JO  - Proceedings of the National Academy of Sciences
DO  - 10.1073/pnas.2608835123
UR  - https://doi.org/10.1073/pnas.2608835123
AB  - Interferon-stimulated genes (ISGs) comprise a program of immune effectors important for host immune defense. When uncontrolled, ISGs play a central role in interferonopathies and other inflammatory diseases. The mechanisms responsible for turning on ISGs are not completely known. By investigating MATRIN3 (MATR3), a nuclear RNA-binding protein mutated in familial ALS, we found that perturbing MATR3 results in elevated expression of ISGs. Using an integrative approach, we elucidate a pathway that leads to activation of cGAS-STING. This outlines a plausible mechanism for pathogenesis in a subset of ALS, and suggests new diagnostic and therapeutic approaches for this fatal disease. One-Sentence Summary Mis-splicing of Tudor Domain Containing 3 ( TDRD3 ) in the absence of MATR3 unleashes R-loops and interferon-stimulated genes.
SN  - 0027-8424
SN  - 1091-6490
ER  -