RNA interference in nematodes and the chance that favored Sydney Brenner

ArticleinJournal of Biology 7(9):34 · December 2008with14 Reads
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.
    • "A study of N. brasiliensis using various delivery methods (Selkirk et al., 2012) also reported a failure to silence genes, other than the originally tested AChE transcripts. It is now recognized that even among Caenorhabditis species, C. elegans is unique in its sensitivity to RNAi (Felix, 2008). This information highlights the challenge in trying to apply RNAi to define gene function in H. contortus and other nematodes. "
    [Show abstract] [Hide abstract] ABSTRACT: The availability of genome and transcriptome data for parasitic nematodes, including Haemonchus contortus, has highlighted the need to develop functional genomics tools. Comparative genomic analysis, particularly using data from the free-living nematode Caenorhabditis elegans, can help predict gene function. Reliable approaches to study function directly in parasitic nematodes are currently lacking. However, gene knockdown by RNA interference (RNAi) is being successfully used in schistosome and planarian species to define gene functions. Lessons from these systems may be applied to improve RNAi in H. contortus. Previous studies in H. contortus and related nematodes demonstrated reliable RNAi-mediated silencing of some genes, but not others. Current data suggest that susceptibility to RNAi in these nematodes is limited to genes expressed in sites accessible to the environment, such as the gut, amphids and excretory cell. Therefore, RNAi is functional in H. contortus, but improvements are needed to develop this system as a functional genomics platform. Here, we summarize RNAi studies on H. contortus and discuss the optimization of RNA delivery and improvements to culture methods to enhance larval development, protein turnover and the induction of phenotypic effects in vitro. The transgenic delivery of RNA or dominant-negative gene constructs and the recently developed CRISPR/Cas genome-editing technique are considered as potential alternative approaches for gene knockout. This is a key time to devote greater effort in progressing from genome to function, to improve our understanding of the biology of Haemonchus and identify novel targets for parasite control.
    Chapter · Apr 2016
    • "In summary, C. elegans has evolved well characterized mechanisms that allow it to (1) take up, (2) amplify, and (3) distribute RNAi effectors throughout the body. Somewhat discouragingly for widespread application of dietary RNA cross-kingdom communication, though, similar mechanisms are unknown not only in distant organisms, but also in species within the same genus (Felix 2008 ). Some other organisms are susceptible to environmental RNAi to a lesser degree (Attasart et al. 2013 ; Bachman et al. 2013 ; Whyard et al. 2009 ; Zhou et al. 2008 ). "
    [Show abstract] [Hide abstract] ABSTRACT: The dietary RNA hypothesis suggests that intact foreign RNAs from food can enter the ingesting organism and potentially function, for example, to silence endogenous transcripts. Studies of mammalian uptake have focused mostly on short RNA molecules known as microRNAs (miRNAs), or “xenomiRs ” to denote their foreign origin. Enthusiasm about absorption and function of plant xenomiRs has been diminished by negative findings and evidence of contamination and experimental design flaws that account for apparently positive results. Nevertheless, some funding groups, regulatory agencies, and scientists remain interested and invested in the topic. Despite the relative lack of accepted evidence for the hypothesis, this interest is likely to continue into the foreseeable future. It may thus be helpful to identify questions that must be answered if, in the future, mammalian dietary RNA uptake and function are to be proven. Here, I examine packaging and stoichiometry considerations for potential plant-mammal RNA communication.
    Chapter · Jan 2016 · Genetics
    • "The reasons for the switch from C. briggsae to C. elegans are now somewhat obscure, but perhaps the most appealing is Brenner's reported quip that he considered C. elegans to be more photogenic (Davies 2002). More likely is that Dougherty pointed out differences in the growth rates of the two species (Félix 2008) and possibly the advantageous behavioral attributes of the Bristol strain of C. elegans , which were later associated with the npr-1 gene. Individuals with the npr-1 gene do not clump or burrow into an agar medium, thus greatly facilitating microscopic observation of behavioral and developmental phenomena. "
    [Show abstract] [Hide abstract] ABSTRACT: Ellsworth Dougherty (1921-1965) was a man of impressive intellectual dimensions and interests; in a relatively short career he contributed enormously as researcher and scholar to the biological knowledge base for selection of Caenorhabditis elegans as a model organism in neurobiology, genetics, and molecular biology. He helped guide the choice of strains that were eventually used, and, in particular, he developed the methodology and understanding for the nutrition and axenic culture of nematodes and other organisms. Dougherty insisted upon a concise terminology for culture techniques and coined descriptive neologisms that were justified by their linguistic roots. Among other contributions, he refined the classification system for the Protista.
    Full-text · Article · Aug 2015
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