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Publication : Drosha as an interferon-independent antiviral factor.

First Author  Shapiro JS Year  2014
Journal  Proc Natl Acad Sci U S A Volume  111
Issue  19 Pages  7108-13
PubMed ID  24778219 Mgi Jnum  J:211074
Mgi Id  MGI:5573097 Doi  10.1073/pnas.1319635111
Citation  Shapiro JS, et al. (2014) Drosha as an interferon-independent antiviral factor. Proc Natl Acad Sci U S A 111(19):7108-13
abstractText  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. Additionally, increased virus infection in the absence of Drosha was not due to a loss of viral small RNAs but, instead, correlated with cleavage of viral genomic RNA and modulation of the host transcriptome. Taken together, we propose that Drosha represents a unique and conserved arm of the cellular defenses used to combat virus infection.
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