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SLIRP promotes autoimmune diseases by amplifying antiviral signaling via positive feedback regulation.
Ku, Doyeong; Yang, Yewon; Park, Youngran; Jang, Daesong; Lee, Namseok; Lee, Yong-Ki; Lee, Keonyong; Lee, Jaeseon; Han, Yeon Bi; Jang, Soojin; Choi, Se Rim; Ha, You-Jung; Choi, Yong Seok; Jeong, Woo-Jin; Lee, Yun Jong; Lee, Kyung Jin; Cha, Seunghee; Kim, Yoosik.
Afiliación
  • Ku D; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
  • Yang Y; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
  • Park Y; Center for RNA Research, Institute of Basic Science, Seoul, 08826, Republic of Korea.
  • Jang D; School of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • Lee N; Department of Oral and Maxillofacial Diagnostic Science, Center for Orphaned Autoimmune Disorders, University of Florida College of Dentistry, Gainesville, Florida, 32610, United States of America.
  • Lee YK; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
  • Lee K; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
  • Lee J; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
  • Han YB; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam, 13488, Republic of Korea.
  • Jang S; Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • Choi SR; R&D Institute, ORGANOIDSCIENCES Ltd., Seongnam, 13488, Republic of Korea.
  • Ha YJ; Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • Choi YS; Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • Jeong WJ; Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • Lee YJ; Department of Otorhinolaryngology - Head & Neck Surgery, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • Lee KJ; Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Cha S; Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • Kim Y; Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
bioRxiv ; 2024 Jun 10.
Article en En | MEDLINE | ID: mdl-38915695
ABSTRACT
The abnormal innate immune response is a prominent feature underlying autoimmune diseases. One emerging factor that can trigger dysregulated immune activation is cytosolic mitochondrial double-stranded RNAs (mt-dsRNAs). However, the mechanism by which mt-dsRNAs stimulate immune responses remains poorly understood. Here, we discover SRA stem-loop interacting RNA binding protein (SLIRP) as a key amplifier of mt-dsRNA-triggered antiviral signals. In autoimmune diseases, SLIRP is commonly upregulated, and targeted knockdown of SLIRP dampens the interferon response. We find that the activation of melanoma differentiation-associated gene 5 (MDA5) by exogenous dsRNAs upregulates SLIRP, which then stabilizes mt-dsRNAs and promotes their cytosolic release to activate MDA5 further, augmenting the interferon response. Furthermore, the downregulation of SLIRP partially rescues the abnormal interferon-stimulated gene expression in autoimmune patients' primary cells and makes cells vulnerable to certain viral infections. Our study unveils SLIRP as a pivotal mediator of interferon response through positive feedback amplification of antiviral signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos