Antagonistic roles between Nibbler and Hen1 modulate piRNA 3' ends in Drosophila

Abstract

In eukaryotes, aberrant expression of transposable elements is detrimental to the host genome. Piwi-interacting RNAs of ∼23 to 30 nucleotides (nt) bound to PIWI-clade Argonaute proteins silence transposons strictly dependent on their sequence complementarity. Hence, a key question in understanding piRNA pathways is to determine mechanisms that modulate piRNA sequences. Here, we identify a protein-protein interaction between Nibbler (Nbr), a 3'-to-5' exoribonuclease and Piwi, linking Nbr activity with piRNA pathways. We show a delicate interplay between Nbr and Hen1, a methyltransferase involved in 2'-O-methylation at 3' terminal nucleotides of piRNAs, connecting two genes with opposing activities in biogenesis of piRNA 3' ends. With age, piRNAs become shorter and less, coupled with de-repression of select TEs. We demonstrate that activities of nbr and hen1 inherently contribute to TE silencing and age-dependent profiles of piRNAs. We propose that antagonistic roles between nbr and hen1 define a mechanism to modulate piRNA 3'ends.