Translin/TRAX complex,also named as C3PO,is evolutionarily conserved and participates in diverse cellular processes in different organisms from yeast to human.C3PO plays a critical role in the activation of RNA-induced silencing complexes by promoting the unwinding and degradation of passenger strand of exogenous siRNAs (exo-siRNAs) in Drosophila and human.Moreover,human C3PO (hC3PO) has been found to broadly repress miRNAs by degrading miRNA precursors.However,the effect of Drosophila melanogaster C3PO (dmC3PO) on endogenous siRNA (endo-siRNA) and miRNA pathways remains unknown.Here,we found that the loss of dmC3PO promoted the accumulation of the passenger strand of esi-2.1 (hp-CG4068B),and resulted in the de-repression of the DNA-damage-response gene mutagensensitive 308 (mus308),which is an endogenous slicer target of esi-2.1 in Drosophila.Moreover,we also found that depletion of dmC3PO increased the accumulation of miR-bantam.Taken together,our findings indicated that dmC3PO not only involves in siRNA pathway triggered by dsRNA,but also regulates the abundance of certain endogenous small RNAs in Drosophila.