4.8 Article

An isoform of Dicer protects mammalian stem cells against multiple RNA viruses

Journal

SCIENCE
Volume 373, Issue 6551, Pages 231-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abg2264

Keywords

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Funding

  1. Francis Crick Institute
  2. Cancer Research UK [FC001136]
  3. UK Medical Research Council [FC001136]
  4. Wellcome Trust [FC001136]
  5. ERC Advanced Investigator grant [AdG 268670]
  6. Wellcome Investigator Award [WT106973MA]
  7. EMBO Long-Term Fellowships [ALTF 536-2108, ALTF 1096-2018]
  8. Marie Sklodowska-Curie Individual Fellowships [832511, 837951]
  9. Marie Curie Actions (MSCA) [832511, 837951] Funding Source: Marie Curie Actions (MSCA)

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The discovery of a Dicer isoform called antiviral Dicer provides protection for tissue stem cells against RNA viruses, shedding light on the molecular regulation of antiviral RNAi in mammalian innate immunity. Different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.
In mammals, early resistance to viruses relies on interferons, which protect differentiated cells but not stem cells from viral replication. Many other organisms rely instead on RNA interference (RNAi) mediated by a specialized Dicer protein that cleaves viral double-stranded RNA. Whether RNAi also contributes to mammalian antiviral immunity remains controversial. We identified an isoform of Dicer, named antiviral Dicer (aviD), that protects tissue stem cells from RNA viruses-including Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-by dicing viral double-stranded RNA to orchestrate antiviral RNAi. Our work sheds light on the molecular regulation of antiviral RNAi in mammalian innate immunity, in which different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.

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