The exonuclease Nibbler regulates age‐associated traits and modulates pi RNA length in D rosophila

Summary Nibbler (Nbr) is a 3′‐to‐5′ exonuclease that trims the 3′end of micro RNA s (mi RNA s) to generate different length patterns of mi RNA s in Drosophila . Despite its effect on mi RNA s, we lack knowledge of its biological significance and whether Nbr affects other classes of small RNA s such as pi RNA s and endo‐si RNA s. Here, we characterized the in vivo function of nbr by defining the Nbr protein expression pattern and loss‐of‐function effects. Nbr protein is enriched in the ovary and head. Analysis of nbr null animals reveals adult‐stage defects that progress with age, including held‐up wings, decreased locomotion, and brain vacuoles, indicative of accelerated age‐associated processes upon nbr loss. Importantly, these effects depend on catalytic residues in the Nbr exonuclease domain, indicating that the catalytic activity is responsible for these effects. Given the impact of nbr on mi RNA s, we also analyzed the effect of nbr on pi RNA and endo‐si RNA lengths by deep‐sequence analysis of libraries from ovaries. As with mi RNA s, nbr mutation led to longer length pi RNA s – an effect that was dependent on the catalytic residues of the exonuclease domain. These analyses indicate a role of nbr on age‐associated processes and to modulate length of multiple classes of small RNA s including mi RNA s and pi RNA s in Drosophila .