Epitranscript transfer, a totipotency regulation operated by repetitive genes

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15808
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Keio University
• Principal Investigator: KOBAYASHI-ISHIHARA Mie 慶應義塾大学, 医学部(信濃町), 助教 (00748337)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 全能性 / 初期胚 / Refee (Gm21312) / 胚性ゲノム活性化 / エピトランスクリプト

Outline of Final Research Achievements

Refee (Gm21312) is an uncharacterized protein that is transiently and specifically expressed in mouse totipotent embryos. In the present research project, the grantee aimed to elucidate the functional significance of Refee in totipotency regulation. The grantee studied Refee-binding transcripts and phenotype of Refee knockdown (KD) embryos. These results showed that Refee mainly binds RNA transcribed from Mouse endogenous retrovirus L to enhance its expression and cytoplasmic distribution. In addition, the grantee found that Refee likely recognizes m6A sites on the transcripts. Refee KD embryos failed to develop beyond the two-cell or four-cell stage as they lack zygotic gene activation (ZGA). ZGA is one of the pivotal events in mammalian totipotent embryos; to activate a newly zygotic genome created by the assembly of maternal and paternal genomes. Our findings suggest that Refee, though an RNA binding protein, plays an essential role in facilitating the zygotic genome function.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

哺乳類の全能性期胚では父方と母方のゲノムが融合して新たなゲノム(胚性ゲノム)が構築され、遺伝子の転写が一気に活性化される時期である。RefeeはRNAの安定性や核外輸送を促進することで、できたての胚性ゲノムを正常に機能させる役割があると考えられた。概して、全能性期特有に発現するRNA結合タンパク質が哺乳類の全能性制御に必須であるという新しい知見を得ることができた。また従来、初期胚の全能性制御には母性因子が重要である事が多々証明されてきたが、本研究結果は胚性因子もその制御に必要であることを示す先駆的なデータとなった。