The sole purpose of the germline is to produce gametes-the vehicles of heritable genetic and epigenetic information. In animals, the development and maintenance of a functional germline and gametes requires the activity of PIWI proteins, germline- expressed Argonaut family members that interact with small RNAs known as piRNAs. The best known function for the piRNA pathway is to protect the genome from invading transposable elements, yet most animals encode multiple PIWI genes that interact with distinct classes of piRNAs, suggesting that piRNA pathways have divergent functions even within an organism. Indeed, piRNAs that derive from unique sequences in the genome are abundantly expressed during pachytene in the mouse testis, but whether they promote or simply correlate with sperm development is unclear. These observations raise many important and unresolved questions that are essential to understanding how piRNA pathways promote germline immortality. We propose studies in three model organisms-worms, flies, and mice-to identify the conserved mechanisms and functions of piRNA pathways in animals.
The piRNA pathway has a conserved and essential function in germline development, but the mechanisms that drive piRNA biogenesis and the targets for these small RNAs are not well understood. The proposed studies use coordinated studies in diverse experimental systems to define conserved components and functions for this pathway, which are likely to directly impact human reproductive health.
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