Mouse MOV10L1 associates with Piwi proteins and is an essential component of the piRNA pathway

Piwi-interacting RNAs (piRNAs) are essential for silencing of transposable elements in the germline but their biogenesis is poorly understood. Here we demonstrate that MOV10L1, a germ cell-specific putative RNA helicase, is associated with Piwi proteins. Genetic disruption of the MOV10L1 RNA helicase domain in mice renders both MILI and MIWI2 devoid of piRNAs. Absence of a functional piRNA pathway in Mov10l1 mutant testes causes loss of DNA methylation and subsequent de-repression of retrotransposons in germ cells. The Mov10l1 mutant males are sterile due to complete meiotic arrest. This is the first mouse mutant that expresses Piwi proteins but lacks piRNAs, suggesting that MOV10L1 is required for piRNA biogenesis and/or loading to Piwi proteins. Overall design: Examination of piRNAs in Mov10l IP and differences in total small RNA profiles in RNA helicase Mov10l+/- and Mov10l-/- mutants.