Understanding of how the cell distinguishes piRNA precursors and transcripts from cellular counterparts

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15051
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: System genome science
• Research Institution: National Institute of Advanced Industrial Science and Technology (2018-2019); Keio University (2017)
• Principal Investigator: Onoguchi Masahiro 国立研究開発法人産業技術総合研究所, 生命工学領域, 産総研特別研究員 (30645297)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: piRNA / PIWI / transposon / RNA binding protein

Outline of Final Research Achievements

piRNA (PIWI-interacting RNA) is required for the suppression of transposons in the germline and disruption of the piRNA pathway leads to infertility. piRNAs are processed from piRNA precursors and key question is how RNAs are selected as piRNA precursors. Previous studies have shown that piRNA precursor have a determinant sequence that is necessary for and sufficient to the piRNA production. However, which proteins are associated with the determinant sequence remains elusive. Here we analyzed the proteins which associate with the piRNA determinant sequence in OSC cells. Using ChIRP-MS method, we identified 192 proteins which interact with the GFP-Flam-1st exon reporter. We found multiple novel proteins with unknown function as well as the proteins those are shown to be associated with PIWI and/or required for piRNA biogenesis. Our data will provide not only promising candidates for key proteins of piRNA precursor selection but also perspective of the whole piRNA biogenesis pathway.

Free Research Field

RNA生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は新しい研究手法を用いることで、piRNA生合成経路の各ステップに重要なタンパク質因子を横断的に明らかにする世界に先駆けた独創的な研究である。本研究は、piRNA生合成の特異性を決める分子メカニズムの理解に貢献し、piRNA生合成に重要な各遺伝子に関するこれまでの研究を線でつなぐ重要な研究である。将来的には不妊治療の基礎研究として創薬や医学への応用と貢献につながることが期待される。