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SINE RNA of the imprinted miRNA clusters mediates constitutive type III interferon expression and antiviral protection in hemochorial placentas.
Wickramage, Ishani; VanWye, Jeffrey; Max, Klaas; Lockhart, John H; Hortu, Ismet; Mong, Ezinne F; Canfield, John; Lamabadu Warnakulasuriya Patabendige, Hiran M; Guzeloglu-Kayisli, Ozlem; Inoue, Kimiko; Ogura, Atsuo; Lockwood, Charles J; Akat, Kemal M; Tuschl, Thomas; Kayisli, Umit A; Totary-Jain, Hana.
Affiliation
  • Wickramage I; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • VanWye J; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Max K; Laboratory for RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
  • Lockhart JH; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Hortu I; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Mong EF; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Canfield J; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Lamabadu Warnakulasuriya Patabendige HM; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Guzeloglu-Kayisli O; Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
  • Inoue K; Bioresource Engineering Division, BioResource Research Center, RIKEN, Tsukuba 305-0074, Ibaraki, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Ibaraki, Japan.
  • Ogura A; Bioresource Engineering Division, BioResource Research Center, RIKEN, Tsukuba 305-0074, Ibaraki, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Ibaraki, Japan.
  • Lockwood CJ; Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
  • Akat KM; Laboratory for RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA; Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Tuschl T; Laboratory for RNA Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
  • Kayisli UA; Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA.
  • Totary-Jain H; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA; USF Heart Institute, University of South Florida, Tampa, FL 33602, USA. Electronic address: totaryjainh@usf.edu.
Cell Host Microbe ; 31(7): 1185-1199.e10, 2023 07 12.
Article in En | MEDLINE | ID: mdl-37315561
ABSTRACT
Hemochorial placentas have evolved defense mechanisms to prevent the vertical transmission of viruses to the immunologically underdeveloped fetus. Unlike somatic cells that require pathogen-associated molecular patterns to stimulate interferon production, placental trophoblasts constitutively produce type III interferons (IFNL) through an unknown mechanism. We demonstrate that transcripts of short interspersed nuclear elements (SINEs) embedded in miRNA clusters within the placenta trigger a viral mimicry response that induces IFNL and confers antiviral protection. Alu SINEs within primate-specific chromosome 19 (C19MC) and B1 SINEs within rodent-specific microRNA cluster on chromosome 2 (C2MC) produce dsRNAs that activate RIG-I-like receptors (RLRs) and downstream IFNL production. Homozygous C2MC knockout mouse trophoblast stem (mTS) cells and placentas lose intrinsic IFN expression and antiviral protection, whereas B1 RNA overexpression restores C2MCΔ/Δ mTS cell viral resistance. Our results uncover a convergently evolved mechanism whereby SINE RNAs drive antiviral resistance in hemochorial placentas, placing SINEs as integral players in innate immunity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: MicroRNAs Limits: Animals / Pregnancy Language: En Journal: Cell Host Microbe Journal subject: MICROBIOLOGIA Year: 2023 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: MicroRNAs Limits: Animals / Pregnancy Language: En Journal: Cell Host Microbe Journal subject: MICROBIOLOGIA Year: 2023 Document type: Article Affiliation country: Estados Unidos