原创力文档an rig-i-like rna helicase mediates antiviral rnai downstream of viral sirna biogenesis in caenorhabditis elegans一个rig-i-like rna解旋酶介导的抗病毒rnai下游的小干扰rna生物起源病毒线虫.pdfVIP
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An RIG-I-Like RNA Helicase Mediates Antiviral RNAi
Downstream of Viral siRNA Biogenesis in Caenorhabditis
elegans
1¤ 2 1 1
Rui Lu , Erbay Yigit , Wan-Xiang Li , Shou-Wei Ding *
1 Department of Plant Pathology Microbiology, University of California, Riverside, California, United States of America, 2 Program in Molecular Medicine, University of
Massachusetts Medical School, Worcester, Massachusetts, United States of America
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 c
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