Mice deficient in either Mili or Miwi-2 have experienced spermatogenic stem cell arrest and those lacking Miwi-2 underwent a degradation of spermatogonia.

First observed in Drosophila, mutant piwi-piRNA pathways led to a direct increase in dsDNA breaks in ovarian germ cells.

The function of the domain is double stranded-RNA-guided hydrolysis of single stranded-RNA that has been determined in the argonaute family of related proteins.

[1] Argonautes, the most well-studied family of nucleic-acid binding proteins, are RNase H-like enzymes that carry out the catalytic functions of the RNA-induced silencing complex (RISC).

This complex binds and cleaves complementary base pairing messenger RNA, destroying it and preventing its translation into protein.

[17] Recent evidence suggests that the functional role of piwi proteins in germ-line determination is due to their capacity to interact with miRNAs.

Components of the miRNA pathway appear to be present in pole plasm and to play a key role in early development and morphogenesis of Drosophila melanogaster embryos, in which germ-line maintenance has been extensively studied.

[22] Although their biogenesis is not yet well understood, piRNAs and Piwi proteins are thought to form an endogenous system for silencing the expression of selfish genetic elements such as retrotransposons and thus preventing the gene products of such sequences from interfering with germ cell formation.