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DDX5 orchestrates RNA homeostasis to ensure oocyte developmental competence

Mengting Wang1,2, Liping Wang3, Qingqing Cai4

  • 1Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signal Transduction and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Nature Communications
|March 12, 2026
PubMed

Insights

The DEAD-box RNA helicase DDX5 is crucial for female fertility. Its absence in oocytes causes sterility by disrupting RNA homeostasis, chromatin remodeling, and meiotic progression.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Genetics

Background:

  • Oocyte development relies on precise control of transcription and RNA metabolism.
  • RNA-binding proteins are key regulators, but their roles in mammalian oogenesis are not fully understood.

Purpose of the Study:

  • To identify key RNA-binding proteins regulating RNA homeostasis in mammalian oocytes.
  • To elucidate the function of the DEAD-box RNA helicase DDX5 in oogenesis and female fertility.

Main Methods:

  • Oocyte-specific gene deletion of DDX5 in mice.
  • Analysis of chromatin remodeling, meiotic progression, and ploidy.
  • Investigation of DDX5's molecular mechanisms in regulating transcription and RNA metabolism.

Main Results:

  • Oocyte-specific deletion of DDX5 resulted in female sterility.
  • Sterility was associated with defective chromatin remodeling, meiotic arrest, aneuploidy, and fertilization failure.
  • DDX5 was found to promote transcription, clear retrotransposon RNAs, and support maternal mRNA storage.

Conclusions:

  • DDX5 is a master regulator essential for maintaining RNA homeostasis in oocytes.
  • DDX5 integrates transcriptional and post-transcriptional processes critical for oocyte competence and female fertility.

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