Somatic and Germline Mechanisms of Small RNA Inheritance

Informazioni relative al progetto

RNAiNHERITANCE

ID dell’accordo di sovvenzione: 101002999

DOI

10.3030/101002999

Data della firma CE 18 Marzo 2021

Data di avvio 1 Settembre 2021

Data di completamento 31 Dicembre 2027

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 997 150,00

Contributo UE

€ 1 997 150,00

Coordinato da

INSTITUT PASTEUR
France

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

Periodo di rendicontazione: 2023-03-01 al 2024-08-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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.