生殖細胞形成とゲノム防御をつなぐ新たな仕組みを解明

Germ cells maintain the species’ genome across generations. PIWI-interacting RNAs (piRNAs) silence transposons using the information of previously invaded transposons, thereby contributing to genome integrity. In the Drosophila ovary, one of the PIWI proteins, Aub, is critical for germ plasm assembly and subsequent piRNA partitioning to the offspring’s germline. In ovaries lacking Tpp, a maternal factor, piRNA production is reduced and Aub localization to the germ plasm is defective, resulting in impaired germ cell formation. Nevertheless, most transposons remain silenced. Therefore, germ cells will only develop when piRNAs are produced in abundance, exceeding the level required for transposon repression. Consequently, the germ plasm contains sufficient piRNAs to comprehensively cover transposon information, thereby ensuring genome integrity in the progeny germline.

Germ cells transmit genetic information to offspring and maintain the genome of the species. In many animals including Drosophila, germ cell formation relies on maternal determinants in the germ plasm. Several proteins present in the germ plasm of oocytes also localize to the perinuclear nuage in nurse cells, where they contribute to the production of PIWI-interacting RNAs (piRNAs). These piRNAs guide the silencing of transposons, thereby protecting the germline genome from invading mobile elements. Aubergine (Aub) is a germ plasm/nuage protein and a piRNA-directed endonuclease that inactivates transposons. Aub is also essential for germ plasm assembly. The Aub-bound piRNAs in the germ plasm are inherited by the progeny germline and serve as templates for piRNA biogenesis in the next generation. Thus, piRNA production in the nurse cell nuage is thought to be coordinated with germ plasm assembly in the oocyte. However, the underlying mechanism remains unclear. Here, we report that a maternal factor, named tiny pole plasm (tpp), mediates this coordination. Tpp is a GTSF1 family PIWI cofactor. In tpp^– ovaries, the production of piRNAs, particularly Aub-bound piRNAs, is defective, resulting in reduced Aub localization to the germ plasm and impaired germ cell formation. Notably, the levels of piRNA production required for proper Aub localization are much higher than those required for transposon silencing. We propose that producing abundant piRNAs beyond what is required for transposon silencing in the ovary promotes germ plasm assembly, thereby enabling the progeny germline to properly silence transposons for species survival.