The successful development and survival of organisms in different environments rely on their ability to regulate gene expression in a precise, timely, and coordinated manner. Genes are not continuously active; instead, they must be turned on or off in specific cells and moments. To achieve this, organisms have evolved sophisticated regulatory systems. Among these, Argonaute proteins, present in several domains of life, play a central regulatory role. They bind to small RNAs to recognize specific messenger RNAs (mRNAs) by sequence complementarity and negatively regulate their expression.
Beyond their regulatory role in animal development, small RNA-mediated silencing can also be inherited across generations. This phenomenon, known as epigenetic inheritance, allows offspring to "remember" and respond to environmental or developmental experiences of their ancestors. However, not all experiences are passed on, nor do these molecular memories persist indefinitely. This raises fundamental questions: How do organisms decide which molecular memories to retain? How long are they maintained? What mechanisms ensure their inheritance?
This project set out to investigate these questions by exploring how nuclear Argonautes and small RNAs can execute their gene silencing and inheritance functions in the germline of Caenorhabditis elegans, a widely used model organism. While the role of nuclear Argonautes in epigenetic inheritance was recognized, the mechanisms remained unclear.
This project aimed to:
1) Identify the factors involved in the maintenance of silencing across generations
2) Decipher the molecular mechanisms underlying small RNA-mediated transcriptional repression
3) Clarify how these regulatory systems work during development and over successive generations.
By deepening our understanding of heritable gene regulation, this research contributes to the broader field of epigenetics and may ultimately inform areas such as developmental biology and intergenerational health.
