RRC ID 5682
Author Lu R, Yigit E, Li WX, Ding SW.
Title An RIG-I-Like RNA helicase mediates antiviral RNAi downstream of viral siRNA biogenesis in Caenorhabditis elegans.
Journal PLoS Pathog
Abstract Dicer ribonucleases of plants and invertebrate animals including Caenorhabditis elegans recognize and process a viral RNA trigger into virus-derived small interfering RNAs (siRNAs) to guide specific viral immunity by Argonaute-dependent RNA interference (RNAi). C. elegans also encodes three Dicer-related helicase (drh) genes closely related to the RIG-I-like RNA helicase receptors which initiate broad-spectrum innate immunity against RNA viruses in mammals. Here we developed a transgenic C. elegans strain that expressed intense green fluorescence from a chromosomally integrated flock house virus replicon only after knockdown or knockout of a gene required for antiviral RNAi. Use of the reporter nematode strain in a feeding RNAi screen identified drh-1 as an essential component of the antiviral RNAi pathway. However, RNAi induced by either exogenous dsRNA or the viral replicon was enhanced in drh-2 mutant nematodes, whereas exogenous RNAi was essentially unaltered in drh-1 mutant nematodes, indicating that exogenous and antiviral RNAi pathways are genetically distinct. Genetic epistatic analysis shows that drh-1 acts downstream of virus sensing and viral siRNA biogenesis to mediate specific antiviral RNAi. Notably, we found that two members of the substantially expanded subfamily of Argonautes specific to C. elegans control parallel antiviral RNAi pathways. These findings demonstrate both conserved and unique strategies of C. elegans in antiviral defense.
Volume 5(2)
Pages e1000286
Published 2009-2-1
DOI 10.1371/journal.ppat.1000286
PMID 19197349
PMC PMC2629121
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics* Caenorhabditis elegans / immunology Caenorhabditis elegans / metabolism Caenorhabditis elegans / virology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / physiology* Epistasis, Genetic Gene Expression Regulation Gene Targeting Genes, Helminth Microscopy, Fluorescence Mutation Nodaviridae / genetics RNA Interference* RNA, Small Interfering / genetics RNA, Small Interfering / metabolism* RNA, Viral / metabolism Replicon
IF 6.218
Times Cited 78
C.elegans tm1329 tm1217 tm1860 tm1637