RNA interference in nematodes and the chance that favored Sydney Brenner

Institut Jacques Monod, CNRS - Universities of Paris 7 and 6, Tour 43, 2 place Jussieu, 75251 Paris cedex 05, France.
Journal of Biology 12/2008; 7(9):34. DOI: 10.1186/jbiol97
Source: PubMed


The efficiency of RNA interference varies between different organisms, even among nematodes. A recent report of successful RNA interference in the nematode Panagrolaimus superbus in BMC Molecular Biology has implications for the comparative study of the functional genomics of nematode species, and prompts reflections on the choice of Caenorhabditis elegans as a model organism.

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    • "RNA interference (RNAi), the process by which exogenous double-stranded RNA (dsRNA) leads to degradation of complementary endogenous RNA, was first discovered and characterized in C. elegans (Fire et al. 1998). Fortuitously, the laboratory strain N2, which is used for the vast majority of research in C. elegans, is highly sensitive to RNAi whereas other strains in the population vary greatly in their RNAi responses (Tijsterman et al. 2002; Felix 2008; Elvin et al. 2011; Felix et al. 2011). The molecular mechanisms underlying RNAi variation are of great importance because of the widespread use of RNAi as a powerful reverse-genetics technique and because of the shared machinery between RNAi and other small RNA biogenesis pathways (e.g., microRNAs). "
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    ABSTRACT: Resolving the genetic complexity of heritable phenotypic variation is fundamental to understanding the mechanisms of evolution and the etiology of human disease. Trait variation amongst isolates from genetically efficient model organisms offers the opportunity to dissect genetic architectures and identify the molecular mechanisms of causation. Here we present a genetic analysis of loss of sensitivity to gene knockdown via exogenous RNA interference in the germline of a wild isolate of the roundworm Caenorhabditis elegans. We find that the loss of RNA interference sensitivity in the wild isolate CB4856 is recessive to the sensitivity of the lab strain N2. A cross of the strains produced F2 with intermediate sensitivities, and the segregation of the trait amongst F2s strongly deviated from a single locus recessive allele expectation. Linkage analysis in recombinant inbred lines derived from CB4856 and N2 identified a single significant locus on chromosome I that includes the argonaute gene ppw-1. The alleles for ppw-1 were unable to explain the sensitivity of eighteen (12.1%) of the recombinant inbred lines. Complementation tests and F2 segregation analysis of these recombinant inbred lines revealed cases of complex epistatic suppression and enhancement of the effects of ppw-1. We conclude that the variation in RNA interference sensitivity between CB4856 and N2 likely involves the non-additive interactions of eight or more genes in addition to ppw-1.
    G3-Genes Genomes Genetics 04/2013; 3(6). DOI:10.1534/g3.113.005785 · 3.20 Impact Factor
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    • "Until recently, the use of bacteria expressing dsRNAs in nematodes was restricted to C. elegans. Even within the Caenorhabditis genus [30]. The use of RNA interference to inhibit the function of 86% of the 19,427 predicted genes of C. elegans [37]. "
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    ABSTRACT: siRNAs (Short interfering RNAs) and miRNAs (microRNAs), which are mediate silencing via distinct mechanisms C. elegans and Homo sapiens. The breaking of a doublestranded RNA (dsRNA) matching a specific gene sequence into short pieces called short interfering RNA, which trigger the degradation of mRNA that matches its sequence. In this review, we discussed the RNA interference with its principle and application in recent biological research areas.
    06/2010; 1(1):09-14. DOI:10.9735/0976-0482.1.1.9-14
  • Value in Health 11/2005; 8(6). DOI:10.1016/S1098-3015(10)67592-4 · 3.28 Impact Factor
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