<i>MATRIN3</i> deficiency triggers autoinflammation via cGAS-STING activation.

Islam, Zohirul; Polash, Ahsan; Suzawa, Masataka; Chim, Bryan; Kuhn, Skyler; Sultana, Sabrina; Cutrona, Nicholas; Smith, Patrick T; Kabat, Juraj; Ganesan, Sundar; Foroushani, Amir; Hafner, Markus; Muljo, Stefan A

MATRIN3 deficiency triggers autoinflammation via cGAS-STING activation.

Islam, Zohirul; Polash, Ahsan; Suzawa, Masataka; Chim, Bryan; Kuhn, Skyler; Sultana, Sabrina; Cutrona, Nicholas; Smith, Patrick T; Kabat, Juraj; Ganesan, Sundar; Foroushani, Amir; Hafner, Markus; Muljo, Stefan A.

Afiliación

Islam Z; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.
Polash A; RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease (NIAMS), NIH; Bethesda, Maryland 20892, USA.
Suzawa M; RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease (NIAMS), NIH; Bethesda, Maryland 20892, USA.
Chim B; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.
Kuhn S; Integrated Data Sciences Section, Research Technologies Branch (RTB), NIAID, NIH; Bethesda, Maryland 20892, USA.
Sultana S; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.
Cutrona N; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.
Smith PT; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.
Kabat J; Biological Imaging Section, RTB, NIAID, NIH; Bethesda, Maryland 20892, USA.
Ganesan S; Biological Imaging Section, RTB, NIAID, NIH; Bethesda, Maryland 20892, USA.
Foroushani A; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.
Hafner M; RNA Molecular Biology Laboratory, National Institute for Arthritis and Musculoskeletal and Skin Disease (NIAMS), NIH; Bethesda, Maryland 20892, USA.
Muljo SA; Integrative Immunobiology Section, Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); Bethesda, Maryland 20892, USA.

bioRxiv ; 2024 Apr 02.

Article en En | MEDLINE | ID: mdl-38712171

ABSTRACT

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.

Palabras clave

R-loops; RNA-DNA hybrids; RNA-binding proteins; gene expression programs; gene regulatory networks; inflammation; interferon-stimulated genes; nonsense-mediated decay; post-transcriptional regulation; splicing

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