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RTCB is essential for early mouse embryogenesis.

Yu-Qi Chen1, Mei He1, Ran Li1

  • 1Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Jinan, Shandong Province, China.

Biology of Reproduction
|January 12, 2026
PubMed
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RNA ligase RTCB is essential for early mouse development. Its absence causes embryonic lethality by disrupting gastrulation, highlighting a critical YY1-RTCB-NUSAP1 pathway for cell proliferation.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB) is a conserved RNA ligase with known physiological roles.
  • The specific function of RTCB in mammalian reproduction and early embryogenesis remains largely unexplored.

Purpose of the Study:

  • To investigate the role of RTCB in mouse embryonic development, particularly during gastrulation.
  • To elucidate the molecular mechanisms underlying RTCB's function in early embryogenesis.

Main Methods:

  • Generation of a conditional Rtcb knockout mouse model using the Ddx4-Cre system.
  • Histology, immunohistochemistry, and quantitative PCR for analyzing embryonic tissues.
  • Analysis of published single-cell RNA sequencing (scRNA-seq) data.
Keywords:
NUSAP1RTCBYY1cell proliferationembryonic lethality

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  • NIH 3T3 cell experiments to assess mRNA stability upon Rtcb knockdown.

    • Main Results:

    • Complete absence of viable Rtcb-/- offspring indicated embryonic lethality before birth.
    • Rtcb knockout led to gastrulation failure around embryonic day 6.5 (E6.5).
    • Gastrulation failure was associated with reduced cell proliferation and increased apoptosis.
    • NUSAP1 (nucleolar and spindle-associated protein 1) mRNA stability was affected by Rtcb levels, suggesting NUSAP1 acts downstream of RTCB.
    • A spatiotemporal coordination was observed between transcription factor YY1 (Yin-Yang-1), Rtcb, and Nusap1 during early embryogenesis (E3.5-E7.5).

    Conclusions:

    • RTCB is indispensable for successful early mouse embryogenesis.
    • A novel regulatory axis involving YY1, RTCB, and NUSAP1 is proposed to maintain adequate cell proliferation for gastrulation.
    • Disruption of this YY1-RTCB-NUSAP1 pathway leads to gastrulation failure and embryonic lethality.