Identification of host factors that regulate Alu retrotransposition

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19219
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Institute of Physical and Chemical Research (2023); Kyoto University (2021-2022)
• Principal Investigator: Miyoshi Tomoichiro 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (60378841)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: Alu / レトロトランスポゾン / 転移 / LINE-1 / ゲノム

Outline of Final Research Achievements

Human Alu retrotransposon is a non-coding mobile genetic element and can mobilize through the genome using L1 reverse transcriptase; however, the mechanisms and regulators of this genome editing process are poorly understood. To apply the Alu retrotransposition reporter system to a wider range of cell lines for future research and to perform a genetic screening to identify its regulators, we developed a method to visualize Alu retrotransposition using EGFP, a fluorescent protein, and succeeded in measuring Alu retrotransposition by this fluorescent protein with FACS analysis. In addition to the lists already obtained for the L1 ORF2 complex by mass spectrometry, which may include potential Alu regulators, we are now ready to conduct a genetic screening using an Alu-EGFP reporter to search for its regulators.

Free Research Field

分子遺伝学、生化学

Academic Significance and Societal Importance of the Research Achievements

Aluは、少なく見積もっても20人に1人の割合で新規の転移を引き起こし、場合によっては疾患原因となる遺伝子変異を伴う。しかし現生人類でも転移を繰り返すAluの転移機構は殆どわかっておらず、その制御因子を同定・解析することは、我々のゲノムの成り立ちや、発生過程および環境変動によって変化するゲノムの性質を知る上で極めて重要である。新たに開発したAlu-EGFPレポーターはソーティング技術への応用のみならず、生体内にも導入することも可能であるため、将来、Aluが引き起こすゲノム不安定化を軽減する手法や、転移を人為的に制御する技術の開発にも貢献できるだろう。