biostudies-literatureShapiro JSNIAID NIH HHS7108-13https://www.ebi.ac.uk/biostudies/studies/S-EPMC4024876biostudies-literatureUnknown111(19)Utilization of antiviral small interfering RNAs is thought to be largely restricted to plants, nematodes, and arthropods. In an effort to determine whether a physiological interplay exists between the host small RNA machinery and the cellular response to virus infection in mammals, we evaluated antiviral activity in the presence and absence of Dicer or Drosha, the RNase III nucleases responsible for generating small RNAs. Although loss of Dicer did not compromise the cellular response to virus infection, Drosha deletion resulted in a significant increase in virus levels. Here, we demonstrate that diverse RNA viruses trigger exportin 1 (XPO1/CRM1)-dependent Drosha translocation into the cytoplasm in a manner independent of de novo protein synthesis or the canonical type I IFN system. AdditiProceedings of the National Academy of Sciences of the United States of AmericaDrosha as an interferon-independent antiviral factor.PMC4024876R01AI095500R01 AI095500R01AI074951R01 AI074951T32 AI007647AI07647Schmid SCherry StenOever BRShim JVAguado LCShapiro JSYasunaga ASachs DSabin LRfalseDrosha as an interferon-independent antiviral factor.Utilization of antiviral small interfering RNAs is thought to be largely restricted to plants, nematodes, and arthropods. In an effort to determine whether a physiological interplay exists between the host small RNA machinery and the cellular response to virus infection in mammals, we evaluated antiviral activity in the presence and absence of Dicer or Drosha, the RNase III nucleases responsible for generating small RNAs. Although loss of Dicer did not compromise the cellular response to virus infection, Drosha deletion resulted in a significant increase in virus levels. Here, we demonstrate that diverse RNA viruses trigger exportin 1 (XPO1/CRM1)-dependent Drosha translocation into the cytoplasm in a manner independent of de novo protein synthesis or the canonical type I IFN system. Additi2014-01-01T00:00:00Z2014 May2025-04-05T13:37:38.862Z2019-03-27T01:28:27ZS-EPMC40248762477821910.1073/pnas.1319635111