Somatic and Germline Mechanisms of Small RNA Inheritance

Project Information

RNAiNHERITANCE

Grant agreement ID: 101002999

DOI

10.3030/101002999

EC signature date 18 March 2021

Start date 1 September 2021

End date 31 December 2027

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 997 150,00

EU contribution

€ 1 997 150,00

Coordinated by

INSTITUT PASTEUR
France

Periodic Reporting for period 2 - RNAiNHERITANCE (Somatic and Germline Mechanisms of Small RNA Inheritance)

Reporting period: 2023-03-01 to 2024-08-31

Summary of the context and overall objectives of the project

It was long thought that only mutations in germline DNA could affect subsequent generations – future progeny were thought to be insulated from the environmental conditions experienced by parents. However, recent fascinating discoveries have challenged this notion. There is mounting evidence across different species indicating that an animal’s experiences can alter the contents of their germ cells, thereby influencing their offspring and future generations.
A key outstanding question is how gametes acquire this environmental information. In particular, can somatic cells communicate environmental information to the germline?
In this ERC project, we focus on small pieces of RNA, called small RNAs, which can carry information about an individual's experiences and environmental factors. These small RNAs can be transmitted to future generations, potentially influencing the expression of their genes. Our project is uncovering the mechanisms by which these small RNAs transmit information from the soma to the germline and the potential implications for inheritance and disease.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

While it is known that small RNAs in germline cells can influence trait inheritance, it is unclear if endogenous small RNAs from somatic tissues can be passed to the next generation.
In our ERC project, we explored the possibility of small RNA transmission via yolk in the nematode Caenorhabditis elegans. Yolk, synthesized in the soma, is transported to oocytes, providing nutrients to embryos. We found that miRNAs produced in the mother’s intestine are selectively enriched in the yolk and transported to embryos, forming part of the inherited maternal miRNA pool. These yolk-enriched miRNAs, regulated by maternal age and stress, influence gene expression and stress resilience during larval development. We also show that these miRNAs, rather than the yolk itself, are necessary for conferring stress resilience to offspring.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our results challenge the view of yolk as merely a nutrient source, suggesting it also serves as a carrier of epigenetic information. This research provides the first evidence of miRNA movement from the soma to the germline and demonstrates that inherited yolk-enriched miRNAs are crucial for modulating stress responses in progeny. This represents a significant example of soma-to-germline miRNA transfer essential for heritable stress resilience and environmental adaptation. We are also exploring the possibility that histone modifications, another epigenetic mechanism known to transmit information across generations, can also transmit environmental information acquired from the soma.