cell formation. Similar observations were made with the mouse homologs of PIWI, MILI, MIWI and MIWI2. These homologs are known to be present in spermatogenesis. Miwi is expressed in various stages of spermatocyte formation and spermatid elongation where Miwi2 is expressed in Sertoli cells. Mice deficient in either Mili or Miwi-2 have experienced spermatogenic stem cell arrest and those lacking Miwi-2 underwent a degradation of spermatogonia. The effects of piwi proteins in human and mouse germlines seems to stem from their involvement in translation control as Piwi and the small noncoding RNA, piwi-interacting RNA (piRNA), have been known to co-fractionate polysomes. The piwi-piRNA pathway also induces heterochromatin formation at centromeres, thus affecting transcription. The piwi-piRNA pathway also appears to protect the genome. First observed in Drosophila, mutant piwi-piRNA pathways led to a direct increase in dsDNA breaks in ovarian germ cells. The role of the piwi-piRNA pathway in transposon silencing may be responsible for the reduction in dsDNA breaks in germ cells. Role in RNA interference The piwi domain is a protein domain found in piwi proteins and a large number of related nucleic acid-binding proteins, especially those that bind and cleave RNA. 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. 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). In the well-known cellular process of RNA interference, the argonaute protein in the RISC complex can bind both small interfering RNA (siRNA) generated from exogenous double-stranded RNA and microRNA (miRNA) generated from endogenous non-coding RNA, both produced by the ribonuclease Dicer, to form an RNA-RISC complex. This complex binds and cleaves complementary base pairing messenger RNA, destroying it and preventing its translation into protein. Crystallised piwi domains have a conserved basic binding site for the 5' end of bound RNA; in the case of argonaute proteins binding siRNA strands, the last unpaired nucleotide base of the siRNA is also stabilised by base stacking-interactions between the base and neighbouring tyrosine residues. 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,