RRC ID 45981
Author Guo X, Zhang R, Wang J, Lu R.
Title Antiviral RNA silencing initiated in the absence of RDE-4, a double-stranded RNA binding protein, in Caenorhabditis elegans.
Journal J Virol
Abstract Small interfering RNAs (siRNAs) processed from double-stranded RNA (dsRNA) of virus origins mediate potent antiviral defense through a process referred to as RNA interference (RNAi) or RNA silencing in diverse organisms. In the simple invertebrate Caenorhabditis elegans, the RNAi process is initiated by a single Dicer, which partners with the dsRNA binding protein RDE-4 to process dsRNA into viral siRNAs (viRNAs). Notably, in C. elegans this RNA-directed viral immunity (RDVI) also requires a number of worm-specific genes for its full antiviral potential. One such gene is rsd-2 (RNAi spreading defective 2), which was implicated in RDVI in our previous studies. In the current study, we first established an antiviral role by showing that rsd-2 null mutants permitted higher levels of viral RNA accumulation, and that this enhanced viral susceptibility was reversed by ectopic expression of RSD-2. We then examined the relationship of rsd-2 with other known components of RNAi pathways and established that rsd-2 functions in a novel pathway that is independent of rde-4 but likely requires the RNA-dependent RNA polymerase RRF-1, suggesting a critical role for RSD-2 in secondary viRNA biogenesis, likely through coordinated action with RRF-1. Together, these results suggest that RDVI in the single-Dicer organism C. elegans depends on the collective actions of both RDE-4-dependent and RDE-4-independent mechanisms to produce RNAi-inducing viRNAs. Our study reveals, for the first time, a novel siRNA-producing mechanism in C. elegans that bypasses the need for a dsRNA-binding protein.
Volume 87(19)
Pages 10721-9
Published 2013-10-1
DOI 10.1128/JVI.01305-13
PII JVI.01305-13
PMID 23885080
PMC PMC3807410
MeSH Animals Animals, Genetically Modified Antiviral Agents / pharmacology* Blotting, Northern Caenorhabditis elegans / virology* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Host-Pathogen Interactions* Insect Viruses / genetics* RNA Interference* RNA Replicase / genetics RNA Replicase / metabolism RNA, Double-Stranded / genetics RNA, Double-Stranded / metabolism RNA, Small Interfering / genetics RNA, Viral / genetics RNA-Binding Proteins / antagonists & inhibitors RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism*
IF 4.501
Times Cited 11
C.elegans tm1329 tm1429