The exonuclease Nibbler regulates age‐associated traits and modulates piRNA length in Drosophila. Issue 3 (6th March 2015)

• Record Type: Journal Article
• Authors: Feltzin, Virzhiniya L.; Khaladkar, Mugdha; Abe, Masashi; Parisi, Michael; Hendriks, Gert‐Jan; Kim, Junhyong; Bonini, Nancy M.
• Is Part Of: Aging cell. Volume 14:Issue 3(2015:Jun.)
• Page Start: 443
• Page End: 452
• Publication Date: 2015-03-06
• Subjects: Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12323
• Languages: English
• ISSNs: 1474-9718

Abstract

<abstract abstract-type="main" id="acel12323-abs-0001"> <title>Summary</title> <p>Nibbler (Nbr) is a 3′‐to‐5′ exonuclease that trims the 3′end of microRNAs (miRNAs) to generate different length patterns of miRNAs in <italic>Drosophila</italic>. Despite its effect on miRNAs, we lack knowledge of its biological significance and whether Nbr affects other classes of small RNAs such as piRNAs and endo‐siRNAs. Here, we characterized the <italic>in vivo</italic> function of <italic>nbr</italic> by defining the Nbr protein expression pattern and loss‐of‐function effects. Nbr protein is enriched in the ovary and head. Analysis of <italic>nbr</italic> 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 <italic>nbr</italic> 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 <italic>nbr</italic> on miRNAs, we also analyzed the effect of <italic>nbr</italic> on piRNA and endo‐siRNA lengths by deep‐sequence analysis of libraries from ovaries. As with miRNAs, <italic>nbr</italic> mutation led to longer length piRNAs – an effect that was dependent on the catalytic residues of the exonuclease domain. These analyses indicate a role of <italic>nbr</italic> on age‐associated processes and to modulate length of multiple classes of small RNAs including miRNAs and piRNAs in <italic>Drosophila</italic>.</p> </abstract>