Endoribonucleases are critical enzymes that mediate RNA cleavage, playing a central role in gene
regulation and cellular defense. Their activity must be precisely controlled to remove harmful
RNAssuch as those derived from viruses and transposonswithout unintentionally degrading
essential transcripts. In the germline, transposon silencing is vital for genome stability and fertility.
The nematode C. elegans provides a powerful model to study this process, with RDE-8 functioning
as a key endoribonuclease that targets transposon-derived RNAs. Loss of RDE-8 results in
transposon mobilization, leading to genomic instability and sterility.
My postdoctoral research investigates the molecular mechanisms that govern RDE-8 specificity
and regulation. Using biochemical and structural approaches (cryo-EM, X-ray crystallography)
complemented by computational modeling, I have identified a mechanism that maintains RDE-8
in an inactive state to prevent aberrant RNA cleavage. My current work focuses on elucidating
how protein cofactors facilitate RDE-8s activation with spatiotemporal precision.
Orthologous endoribonucleases in humans also contribute to cellular defense. Understanding
how RDE-8 is regulated in C. elegans could reveal conserved principles of nuclease control with
broader implications for RNA metabolism and genome stability.