Role of retrotransposons in early embryonic development and totipotency control

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21507
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: Keio University
• Principal Investigator: MURANO Kensaku 慶應義塾大学, 医学部(信濃町), 講師 (80535295)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: レトロトランスポゾン / 初期胚発生 / LINE-1

Outline of Final Research Achievements

The host defense mechanism against LINE-1, a retrotransposon highly expressed during early embryogenesis, remains elusive. We identified TDP-43 as a protein interacting with LINE-1 ORF1 protein from cell extract of a two-cell stage-like cell derived from mouse ES cells. We tried to knock down TDP-43 expression by injecting siRNA into fertilized mouse eggs. TDP-43 knockdown significantly increased LINE-1 copy number on the mouse genome. These results indicate that TDP-43 contributes to genome integrity by suppressing LINE-1, which is de-repressed during early embryogenesis.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

LINE-1はマウスゲノムの約20%を占め、ゲノム上に自分自身のコピーを増やしていく性質を持つレトロトランスポゾンである。初期胚発生過程においてLINE-1は高発現するが、その生物的な意義や、宿主への影響についての研究はまだ少ない。本研究の成果により、TDP-43は初期胚発生の過程で脱抑制されるLINE-1の転移活性を抑制し、ゲノム恒常性の維持に寄与していていることが示された。本研究によりトランスポゾンと宿主の共生関係の一端が明らかとなった。