Somatic and Germline Mechanisms of Small RNA Inheritance

Projektinformationen

RNAiNHERITANCE

ID Finanzhilfevereinbarung: 101002999

DOI

10.3030/101002999

EK-Unterschriftsdatum 18 März 2021

Startdatum 1 September 2021

Enddatum 31 Dezember 2027

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 997 150,00

EU-Beitrag

€ 1 997 150,00

Koordiniert durch

INSTITUT PASTEUR
France

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

Berichtszeitraum: 2023-03-01 bis 2024-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.