Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi.

By F. Simmer, M. Tijsterman, S. Parrish, S. Koushika, M. Nonet, Andrew Fire, J. Ahringer, Ronald H. A. Plasterk. Current Biology, 2002

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RNA interference (RNAi) is a broadly used reverse genetics method in C. elegans. Unfortunately, RNAi does not inhibit all genes. We show that loss of function of a putative RNA-directed RNA polymerase (RdRP) of C. elegans, RRF-3, results in a substantial enhancement of sensitivity to RNAi in diverse tissues. This is particularly striking in the nervous system; neurons that are generally refractory to RNAi in a wild-type genetic background can respond effectively to interference in an rrf-3 mutant background. These data provide the first indication of physiological negative modulation of the RNAi response and implicate an RdRP-related factor in this effect. The rrf-3 strain can be useful to study genes that, in wild-type, do not show a phenotype after RNAi, and it is probably the strain of choice for genome-wide RNAi screens.

Subfields: Aging, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/940d66a1fdc725341743ad91e6e860f87fdea517

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Citations in the corpus

Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. (2005, methodology): “The RNAi hypersensitive strain rrf-3 ( Simmer et al., 2002 ) was used for feeding RNAi experiments targeting xrn-1 or Y48B6A.3.”
Guidelines on nicotine dose selection for in vivo research (2007, background): “While neurons have generally proven resistant to RNAi, new hypersensitive strains, such as the RNA-directed RNA polymerase mutant rrf-3, appear to overcome this problem (Simmer et al. 2002).”
Mechanisms of gene silencing by double-stranded RNA (2004, neutral): “The presumably inactive RdRP-family protein RRF-3 (ref”
Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology (2008, background): “Strategies to improve RNAi efficiency, especially in neurons, were further developed (Esposito et al., 2007; Lee et al., 2006; Simmer et al. 2002, 2003; Tabara et al., 2002; Tops et al., 2005).”
Specialization and evolution of endogenous small RNA pathways (2007, background): “elegans mutants with an enhanced RNAi response ( eri mutants”
Genome-Wide RNAi of C. elegans Using the Hypersensitive rrf-3 Strain Reveals Novel Gene Functions (2003, background): “A more detailed study of RNAi sensitivity of rrf-3 mutants using a set of 80 genes showed that rrf-3 is generally more sensitive to RNAi than wild-type worms (Simmer et al. 2002).”
SGS3 and SGS2/SDE1/RDR6 are required for juvenile development and the production of trans-acting siRNAs in Arabidopsis. (2004, background): “RdRPs that participate in PTGS/RNAi have also been described in Caenorhabditis elegans (Smardon et al. 2000; Sijen et al. 2001; Simmer et al. 2002), Neurospora crassa (Cogoni and Macino 1999; Catalanotto et al. 2002; Shiu and Metzenberg 2002), Schizosaccharomyces pombe (Volpe et al. 2002, 2003) and…”
Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. (2008, positive): “(E) In the RNAi-sensitive rrf-3 background (Simmer et al., 2002), the life-span increase seen in daf-2(e1368) is comparably suppressed by either skn-1 or skn-1a/c RNAi.”
A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans (2004, background): “elegans , the RNA-dependent RNA polymerase encoded by rrf-3 , shows identical pleiotropic phenotypes, suggesting that even these limited pleiotropies are probably a consequence of a defect in the siRNase (or possibly microRNase) function of ERI-1 and not in the processing of unrelated cellular mRNA”