Decipher the mechanisms of small antisense RNA biogenesis and inheritance
How small RNAs are inherited from one generation to another and how are they maintained across generations?
In the research project, we are exploring how small RNAs are also inherited from the germline to the zygote to transmit heritable information. An important feature of all the germline small RNAs in C. elegans is that they are generated by an enzyme called RNA-dependent RNA polymerase, which uses mRNAs as templates to synthesize antisense small RNAs. Therefore, the mRNA template is a fundamental molecule that is also required to be inherited in the zygote to synthesize new small RNAs in the next generation.
Recent work from our lab has shown that the maternal mRNA templates are globally degraded in the embryos during the maternal to zygotic transition (1). However, we have noticed that some of these maternal mRNAs are not degraded but retained in very specific organelles in embryos, called germ granules. These germ granules are phase-separated membraneless organelles surrounding the nuclear membrane that are inherited from the germline to the embryo and segregate with the germline blastomere (2-4). They also contain the enzymes to produces small RNAs and the Argonaute proteins that load the small RNAs (2).
Therefore, we will dissect the role of these organelles in delivering and protecting the mRNAs which may be used as templates by the RNA-dependent RNA polymerase enzyme. This would be the mechanisms that allows the de novo production of germline small RNAs in the embryo, and ensure the inheritance of these molecules from one generation to another.
1. Quarato et al., Nature Communications (2021). doi:10.1038/s41467-021-21691-6
2. Wan, G. et al. Nature (2018). doi:10.1038/s41586-018-0132-0
3. Ouyang, J. P. T. et al. Dev. Cell (2019). doi:10.1016/j.devcel.2019.07.026
4. Dodson, A. E. & Kennedy, S. Dev. Cell (2019). doi:10.1016/j.devcel.2019.07.025