Discover the principles of soma-to-germline RNA transfer and its biological functions

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How small RNAs travels from somatic tissues and organs to the germline?

Small RNAs produced in C. elegans neurons can trigger the production of germline small RNAs, which regulate germline genes and transmit learned behavior transgenerationally (1). However, the underlying mechanisms, such as whether the germline acquires RNAs or other molecules from the soma, remain unclear. Soma-to-germline RNA transfer occurs in mouse: small RNAs in sperm are acquired through extracellular vesicles (EVs) from the epididymis (2–4). Interestingly, dsRNA injected into the body cavity of C. elegans can also travel in EVs derived from intestinal cells, which are usually transported directly to oocytes for gut-to-yolk biomass conversion (5,6). Based on these striking observations, we hypothesize that an EV-mediated exchange of RNAs occurs between somatic and germ cells. Building on these findings, we propose to investigate (i) to what extent endogenous dsRNAs and/or other types of small RNAs are delivered from the soma to the germline though EVs, (ii) the molecular mechanisms involved in this process, (iii) the genes that are regulated by this process, and (iv) the potential transgenerational functions of circulating RNA molecules, such as during the stress responses. 

Our study will elucidate the upstream factors and the downstream effectors responsible for this small RNA trafficking, from the soma to the germline to the next generation. We also propose to study the function of this RNA communication system and its possible involvement in transmitting the memory of stress responses across generations.

References

1. Posner, R. et al. Cell (2019). doi:10.1016/j.cell.2019.04.029

2. Conine, C.C. et al., Dev. Cell (2018). doi:10.1016/j.devcel.2018.06.024

3. Sharma, U. et al. Dev. Cell (2018). doi:10.1016/j.devcel.2018.06.023

4. Sharma, U. et al. Science (80-. ). (2016). doi:10.1126/science.aad6780

5. Wang, E. & Hunter, C. P. Genetics(2017). doi:10.1534/genetics.117.300067

6. Marré, J., et al., Proc. Natl. Acad. Sci. U. S. A. (2016). doi:10.1073/pnas.1608959113