piRNAs and their involvement in male germline development in mice

Piwi‐interacting RNAs (piRNAs) are a class of small non‐coding RNAs expressed in the animal gonads. They are implicated in silencing the genome instability threat posed by mobile genetic elements called transposons. Unlike other small RNAs, which use double‐stranded precursors, piRNAs seem to arise from long single‐stranded precursor transcripts expressed from discrete genomic regions. In mice, the Piwi pathway is essential for male fertility, and its loss‐of‐function mutations affect several distinct stages of spermatogenesis. While this small RNA pathway primarily operates post‐transcriptionally, it also impacts DNA methylation of target retrotransposon loci, representing an intriguing model of RNA‐directed epigenetic control in mammals. Remarkably the Piwi pathway components are specifically localized at germinal granule/nuage, an evolutionarily conserved but still enigmatic ribonucleoprotein compartment in the germline. The inaccessibility of the germline for easy experimental manipulation has meant that this class of RNAs has remained enigmatic. However, recent advances in the use of cell culture models and cell‐free systems have greatly advanced our understanding. In this review, we briefly summarize our current understanding of the Piwi pathway, focusing on its developmental regulation, piRNA biogenesis and key function in male germline development from fetal spermatogonial stem cell stage to postnatal haploid spermiogenesis in mice.