[
International Worm Meeting,
2015]
In all domains of life, non-coding RNAs regulate gene expression1. This mechanism called RNA interference has been a powerful technique in basic research over the last two decades. Today, RNAi enters the hospital and RNAi therapeutics have the potential to revolutionize drug development 2. One of the key challenges for RNAi therapeutics remains efficient RNA delivery. RNAi effectors move from cell to cell and spread through tissues in invertebrates, plants and fungi 3. In the mammalian system, extracellular vesicles (ECVs) shuttle RNA between cells 4. Recently, Wang et al. showed that C. elegans secrets ECVs in to the environment, possibly delivering RNA from animal to animal 5. However, the presents of RNA in ECVs and the molecular mechanism of mobile RNA between individuals is not known in any system. Here, I propose a purification protocol for extracellular vesicle (ecv)RNA released by the model organism C. elegans. Using this protocol, we sequenced small RNAs and RNAs from males, hermaphrodites and males deficient in vesicle release. A subset of small non-coding RNAs and messenger RNAs were enriched in male ECVs. This work characterizes the ecvRNA profile of C. elegans and may help to elucidate the social role of RNAs and has the potential to inform new approaches to RNAi therapy.1. Cech, T. R. & Steitz, J. A. The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157, 77-94 (2014).2. Ozcan, G., Ozpolat, B., Coleman, R. L., Sood, A. K. & Lopez-Berestein, G. Preclinical and clinical development of siRNA-based therapeutics. Adv. Drug Deliv. Rev. (2015). doi:10.1016/j.addr.2015.01.0073. Sarkies, P. & Miska, E. A. Molecular biology. Is there social RNA? Science 341, 467-468 (2013).4. Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654-659 (2007).5. Wang, J. et al. C. elegans ciliated sensory neurons release extracellular vesicles that function in animal communication. Curr. Biol. 24, 519-25 (2014).
Price, Jon, Willis, Alexandra, Stevens, Lewis, Miska, Eric, Fisher, Kinsey, Reinke, Aaron, Burton, Nick, Braukmann, Fabian, Baugh, L. Ryan
[
International Worm Meeting,
2021]
Despite reports of parental exposure to stress promoting adaptations in progeny in diverse organisms, there remains considerable debate over the ecological significance and evolutionary conservation of these multigenerational effects. Here, we investigate four independent examples of intergenerational adaptations to stress in C. elegans - bacterial infection, microsporidia infection, osmotic stress and starvation - across four different Caenorhabditis species. We found that all four intergenerational adaptations to stress are conserved in at least one other species, that the responses and evolutionary conservation patterns are stress specific, and that intergenerational adaptive effects have deleterious trade-offs in mismatched environments. By profiling the intergenerational and transgenerational effects of different stresses on gene expression across species, we identified 3,174 genes that exhibited intergenerational changes in expression in multiple species in response to stress. Furthermore we found that an inversion in the expression of certain stress response genes required for intergenerational adaptations, from increased expression in the offspring of stressed parents to decreased expression in the offspring of stressed parents, correlates with an inversion of an adaptive response to infection in C. elegans and C. kamaaina to a deleterious intergenerational effect in C. briggsae. By contrast, we did not observe any conserved transgenerational changes in gene expression in response to stress, suggesting that the intergenerational effects of stress on offspring gene expression are not maintained transgenerationally. Our results demonstrate that intergenerational responses to stress play a substantial, evolutionarily conserved, and largely reversible role in regulating animal physiology.