Drosha 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. 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.
Department of Microbiology,Icahn Graduate School of Biomedical Sciences, and.
Jillian S
JS
Shapiro
Department of Microbiology.
Sonja
S
Schmid
Department of Microbiology,Icahn Graduate School of Biomedical Sciences, and.
Lauren C
LC
Aguado
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104.
Leah R
LR
Sabin
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104.
Ari
A
Yasunaga
Department of Microbiology.
Jaehee V
JV
Shim
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and.
David
D
Sachs
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104.
Sara
S
Cherry
Department of Microbiology,Icahn Graduate School of Biomedical Sciences, and Benjamin.tenOever@mssm.edu.
Benjamin R
BR
tenOever
D018354:Alphavirus Infections / Q000276:immunology*; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D005347:Fibroblasts / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D028884:Karyopherins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D012367:RNA, Viral / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012845:Sindbis Virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology; D000097606:Exportin 1 Protein
D029721:Drosophila Proteins; D007370:Interferon Type I; D028884:Karyopherins; D035683:MicroRNAs; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D043244:Ribonuclease III; D000097606:Exportin 1 Protein; C572067:MIRN124 microRNA, Drosophila; C493335:drosha protein, Drosophila
RNAi; Rnasen; innate immunity; miRNA; microRNA