The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements.

The combination of Piwi proteins and their associated Piwi-interacting RNAs (piRNAs) mediates epigenetic transposon silencing in animal germlines. Piwi proteins are predicted to be endonucleases, but the significance of this activity had not been demonstrated in vivo. The laboratories of Dnal O'Carroll and Ramesh Pillai have now made mouse models in which residues expected to be critical for nuclease activity in the three mouse Piwi homologues, Mili, Miwi and Miwi2, are mutated. The mutant mice show phenotypic differences. The Mili and Miwi mutants are defective in piRNA production, transposon silencing and fertility, whereas the Miwi2 mutant has normal piRNA levels, seems to undergo piRNA amplification and silences transposons. These studies highlight distinctions between the murine enzymes responsible for piRNA biogenesis.