We study the mechanisms and functions of small RNA silencing in the fruit fly Drosophila melanogaster using genetic, biochemical and bioinformatic approaches.
Three classes of small RNAs, piRNAs, miRNAs and siRNAs, are at the core of a vast RNA silencing biochemical framework in animals. They associate with Argonaute proteins, which they guide to complementary targets. The resulting silencing may occurs by cleavage, destabilization or inhibition of translation of RNA transcripts, or by DNA or histone modifications at complementary loci. Small RNAs are involved in numerous biological processes including gene regulation, defense against exogenous pathogens and endogenous selfish transposons, chromatin and chromosome dynamics and genome rearrangements. The variety of mechanistic and functional outputs reflects the multiplicity of intertwined RNA silencing pathways that potentially interact or compete with each other. We are far from understanding the molecular basis of these variations, as well as their biological impact.
Within this context, we are focusing on two main issues:
- How do siRNA and piRNAs control chromatin structure and epigenetic states?
- How does the miRNA silencing network diversified to control Drosophila development and homeostasis?