Small RNAs in immunity and regulation of giant endogenous viral elements in eukaryotes

In this project, we aim to investigate the role of small RNAs (sRNAs) in defending against giant virus infections. Giant viruses are eukaryotic viruses with exceptionally large genomes, some of which surpass the size of bacterial genomes. Remarkably, giant virus integrations have been found across various eukaryotes, leading to the formation of giant endogenous viral elements (GEVEs). Among the reported GEVEs, the host group (Dr. de Mendoza’s laboratory) has identified a unicellular relative of animals that harbours hundreds of GEVEs—more than any other known eukaryote. This observation suggests that these viral integrations may confer a beneficial role to the host. Although GEVEs are typically transcriptionally silent, the removal of DNA methylation triggers the reactivation of many viral genes, mimicking an infection. Notably, proteins related to sRNA biogenesis are upregulated during this reactivation, indicating that sRNAs may play a role in post-transcriptional silencing of the endogenized viruses, as no viral particles are formed. Based on these findings, we hypothesize that GEVE-derived transcripts generate sRNAs that help defend against future infections.To explore this hypothesis, I will bring my expertise in small RNAs to the host lab, aiming to deepen our understanding of how sRNAs co-evolved with GEVEs and how they may function in immunity against giant viruses. My focus will be on key unicellular eukaryotes that possess the genetic machinery necessary for sRNA processing and show evidence of containing GEVEs. The outcomes of this project have the potential to open a new field of research. If sRNAs are indeed involved in immunity, they could be leveraged to protect these species against new infections. Additionally, we propose various outreach activities to engage the public and highlight the importance of studying the evolution of unicellular eukaryotes and giant viruses.