Elucidation of Shu exclusion in cytoplasmic droplet Yb bodies and its application to droplet-specific proteomes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15056
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hirakata Shigeki 東京大学, 大学院理学系研究科(理学部), 助教 (40844791)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: piRNA / Shutdown / トランスポゾン / 無精子症

Outline of Final Research Achievements

In Drosophila ovarian somatic cells, Shu recruits Piwi to the cytoplasmic granule Yb body, but Shu quickly leaves the granule. In this study, I investigated the mechanism of this process and clarified that repulsion between Shu is important for Shu release. I also found that Shu release is essential for Piwi to leave the Yb body in a later process, and I have identified a region responsible for Shu repulsion. In addition, I found the existence of feedback regulation in the piRNA biogenesis pathway and that a mutation reported in human azoospermia prevents the release of Shu.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、piRNA生合成経路の全容解明、特に、PiwiがpiRNAの生合成過程に応じて細胞内局在を変えていく機構を理解する上で重要である。加えて、Shuの反発に働く領域を同定できたため、今後はこれを応用してYb body特異的近接依存標識法の確立に取り組むことができる。また、当初想定していなかった成果として、ヒト不妊の原因変異がもたらすpiRNA経路の異常について新しい知見が得られた。本成果は医療応用、特に不妊治療への貢献が期待できる。