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The microRNAs miR-302b and miR-372 regulate mitochondrial metabolism via the SLC25A12 transporter, which controls MAVS-mediated antiviral innate immunity.
Yasukawa, Kai; Kinoshita, Daisuke; Yaku, Keisuke; Nakagawa, Takashi; Koshiba, Takumi.
Afiliación
  • Yasukawa K; Department of Biology, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan; Modality Laboratories, Innovative Research Division, Mitsubishi Tanabe Pharma Corp., Fujisawa 251-8555, Japan.
  • Kinoshita D; Department of Biology, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan.
  • Yaku K; Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama 930-0194, Japan.
  • Nakagawa T; Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama 930-0194, Japan; Frontier Research Core for Life Science, University of Toyama, Toyama 930-0194, Japan.
  • Koshiba T; Department of Biology, Faculty of Science, Kyushu University, Fukuoka 819-0395, Japan; Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka 814-0180, Japan. Electronic address: koshiba@kyudai.jp.
J Biol Chem ; 295(2): 444-457, 2020 01 10.
Article en En | MEDLINE | ID: mdl-31767682
MicroRNAs (miRNAs) are small noncoding RNAs that suppress the expression of multiple genes and are involved in numerous biologic functions and disorders, including human diseases. Here, we report that two miRNAs, miR-302b and miR-372, target mitochondrial-mediated antiviral innate immunity by regulating mitochondrial dynamics and metabolic demand. Using human cell lines transfected with the synthetic analog of viral dsRNA, poly(I-C), or challenged with Sendai virus, we found that both miRNAs are up-regulated in the cells late after viral infection and ultimately terminate the production of type I interferons and inflammatory cytokines. We found that miR-302b and miR-372 are involved in dynamin-related protein 1 (DRP1)-dependent mitochondrial fragmentation and disrupt mitochondrial metabolism by attenuating solute carrier family 25 member 12 (SLC25A12), a member of the SLC25 family. Neutralizing the effects of the two miRNAs through specific inhibitors re-established the mitochondrial dynamics and the antiviral responses. We found that SLC25A12 contributes to regulating the antiviral response by inducing mitochondrial-related metabolite changes in the organelle. Structure-function analysis indicated that SLC25A12, as part of a prohibitin complex, associates with the mitochondrial antiviral-signaling protein in mitochondria, providing structural insight into the regulation of the mitochondrial-mediated antiviral response. Our results contribute to the understanding of how miRNAs modulate the innate immune response by altering mitochondrial dynamics and metabolic demand. Manipulating the activities of miR-302b and miR-372 may be a potential therapeutic approach to target RNA viruses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Respirovirus / Virus Sendai / Proteínas de Transporte de Membrana Mitocondrial / MicroARNs / Mitocondrias Límite: Humans Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Respirovirus / Virus Sendai / Proteínas de Transporte de Membrana Mitocondrial / MicroARNs / Mitocondrias Límite: Humans Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos