Over the past several years RNA-based immunity against genomic invaders has been discovered in all branches of life ranging from the CRISPR-Cas systems in bacteria to piRNAs in animals. piRNAs, in Drosophila germline cells are encoded by specific loci called piRNA clusters. These loci establish and maintain memory of “nonself ” by generating small guides to induce an adaptive defense against genomic parasites like transposable elements (TEs). At the heart of this defense mechanism resides a piRNA induced silencing complex (piRISC) which consists of a piRNA and its associated Argonaute protein partner. Within piRISC, the small RNA determines target specificity by base pairing, while its Argonaute partner governs effector activity. The mRNA can be either cleaved in the cytoplasm (PTGS) or bound in the nucleus leading to TGS.
Biogenesis and function of the piRNAs in Drosophila germline cells
In the lab, we are dissecting the biogenesis and the role of piRISC in Drosophila. We have demonstrated that the Argonaute Piwi protein is required during Drosophila embryonic development for the activation of piRNA clusters via the deposition of H3K9me3 repressive marks. Once established in the embryo, this epigenetic mark will be maintained in a Piwi-independent manner during the whole ovarian development.
For our studies we combine fly genetics, proteomics and deep sequencing approaches (small RNA-seq, RNA-seq, ChIP-seq), using molecular and cell biology tools (CRISPR/dCas9).