Activated RNAi does not rescue piRNA pathway deficiency in testes

RNA interference (RNAi) and PIWI-associated RNAs (piRNA) pathways use small RNAs as sequence-specific guides to repress transposable elements. In mice, the loss of Mili, an essential piRNA pathway factor, causes male sterility associated with mobilization of LINE L1 retrotransposons while female mutants remain fertile. At the same time, mouse oocytes have exceptionally active RNAi thanks to an oocyte-specific variant of RNase III Dicer, which efficiently makes small RNAs from long dsRNA substrates. In oocytes of mice lacking functional MILI and the oocyte-specific Dicer variant, we previously observed that L1 retrotransposons are redundantly targeted by both, RNAi and piRNA pathways. To test whether enhanced RNAi may reduce the Mili mutant phenotype in testes, we used transgenic mice ectopically expressing the oocyte-specific Dicer variant during spermatogenesis. We report here that this genetic modification increases siRNA biogenesis and supports RNAi but is not sufficient to reduce spermatogenic defects caused by the loss of Mili. Bulk small RNA-seq of 9 mouse samples, three different tissues in three different genotypes: - Dicerwt/wt spleen, liver, testes - DicerΔHEL1/wt spleen, liver, testes - DicerTg(O-HA) spleen, liver, testes