Trends in Genetics
ReviewEnvironmental RNA interference
Section snippets
Overview of cell autonomous versus non–cell autonomous RNA interference
Exposure of eukaryotic cells to double-stranded RNA (dsRNA) can lead to post-transcriptional degradation of homologous mRNA sequences. Known as RNA interference (RNAi), this process was initially described in the nematode Caenorhabditis elegans and subsequently demonstrated in fungi, plants, insects and animals 1, 2. In many organisms, RNAi seems to be exclusively cell autonomous (i.e. affecting only the cells that generate dsRNA or that are directly exposed to experimentally introduced dsRNA).
Genetic analysis of environmental RNAi in C. elegans
Studies in C. elegans have provided insight into how dsRNA molecules enter an organism from the environment to trigger RNAi. With an impermeable cuticle covering nearly its entire surface, C. elegans is thought to take up dsRNA through the intestinal lumen while feeding. The ingested dsRNAs and resulting silencing signals spread systemically to other cells in the animal. Importantly, these silencing signals can be generated in the absence of target gene expression in the intestine [25]. Thus,
Environmental RNAi in other organisms
In addition to C. elegans, environmental RNAi is observed in several multicellular organisms, including other nematodes, arthropods and cnidarians (e.g. hydra, jellyfish, anemones). Surprisingly, a related nematode C. briggsae cannot perform environmental RNAi, although it can trigger a robust systemic RNAi response to dsRNA injection. Investigating the similarities and differences between these organisms will help to elucidate the mechanisms, function and regulation of environmental RNAi.
Applications of environmental RNAi
Although the mechanisms underlying environmental RNAi remain poorly understood, the process of environmental dsRNA uptake has already been harnessed for important biological applications. Environmental RNAi provides an inexpensive and technically simple method of delivering dsRNA. In particular, this method has revolutionized large-scale RNAi screening and has prompted innovative approaches to agricultural pest control. In the future, we can envision the oral delivery of dsRNA therapeutics in
Concluding remarks and future perspectives
The discovery of RNAi revolutionized our understanding of gene regulation. The more recent descriptions of systemic and environmental RNAi have revealed a novel means of communication between cells. The ability to trigger an RNAi response to dsRNAs in the environment is particularly intriguing as a means of communication between organisms and their environment. Since the initial discovery in C. elegans, environmental RNAi has been observed in a wide range of metazoans and even in some
Acknowledgements
The authors thank Javier Apfeld, Andrea Hinas, Antony Jose, Katerina Ragkousi, Daniel Schott and Lucie Yang for critical comments on the manuscript. This work was supported by grants to C.P.H. from the National Science Foundation (MCB0417102) and the National Institutes of Health (GM069891).
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