TRANSGENERATIONAL SMALL RNA INHERITANCE
Updated: Nov 6, 2022
It is currently unknown whether, how, and to what extent epigenetic information can transmit across generations. Our mission is to discover weird mechanisms of heredity. Indeed, recent discoveries are making the once heretic idea of inheritance of acquired traits relevant again (not the naïve ideas that Lamarck imagined, obviously!). Parental experiences, at least in worms, can affect the progeny’s physiology, sometimes permanently, or at least for multiple generations.
In C.elegans, the mechanisms are being revealed, and the rate of progress is truly exciting. We are interested in inheritance of small RNAs, molecules that are actively shuttled between different tissues, and from the soma to the germline. We discovered that small RNAs are transcribed in response to different environmental stresses (Cell 2011, Cell 2014, Cell 2019, Dev Cell 2022). We showed for the first time that heritable small RNAs are not diluted, since RNA-dependent RNA polymerases amplify the response in the progeny, in every generation (Cell 2011). Moreover, we recently discovered that a systemic feed-back mechanism determines whether to “memorize the epigenetic response” (continue and transmit the ancestral information to additional generations), or whether to terminate the response and “forget” the memory, and rely once again on the hardwired genetic program (for example Cell 2016, Current biology 2017, eLife 2019). We found genes that we dubbed “motek” genes (MOdified Transgenerational Epigenetic Kinetics) that participate in this feedback pathway, constitute a “transgenerational timer”, and affect the duration of heritable silencing (Cell 2016). Recently we have been focusing on elucidating the role of liquid like condensates in transmitting small RNAs across generations in the germ cells cytoplasm (Current Biology 2019). We find that inheritance of small RNAs obeys rules which are completely different but analogous to the rules that govern inheritance of DNA (Mendelian inheritance) (Cell 2020). We previously showed (Genes & Development, 2009) that functional small RNAs and other macromolecules (Nature Methods 2010) can move between interacting human cells (through the immunological synapse) (see also Nature Reviews in Molecular Cell Biology 2022). We are motivated to discover whether the principles that govern epigenetic inheritance in C.elegans hold true also to other animals, including mammals.
Artwork by Leah Houri-Zeevi