Oocyte competence is maintained by m6A methyltransferase KIAA1429-mediated RNA metabolism during mouse follicular

Yue Hu1, Zhangyi Ouyang2, Xuesong Sui1

  • 1State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China.

Insights

KIAA1429 (vir-like m6A methyltransferase-associated protein) is essential for female fertility. Its deficiency in oocytes disrupts follicular development and meiosis, impacting RNA metabolism and oocyte competence.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Epigenetics

Background:

  • KIAA1429 (VIRMA) is a key component of the RNA m6A methyltransferase complex, influencing m6A deposition.
  • Its in vivo function in mammalian RNA m6A regulation remains largely unexplored.

Purpose of the Study:

  • To investigate the role of KIAA1429 in mammalian oocyte development and RNA metabolism in vivo.
  • To determine the impact of KIAA1429 deficiency on female fertility and meiotic progression.

Main Methods:

  • Generation of oocyte-specific Kiaa1429-deficient mice.
  • Analysis of oocyte development, follicular growth, and meiotic maturation.
  • RNA sequencing (RNA-seq) to profile gene expression and alternative splicing.
  • Measurement of m6A levels in oocytes.

Main Results:

  • Kiaa1429 deficiency in oocytes caused female infertility with defective follicular development.
  • Impaired oocytes failed germinal vesicle breakdown (GVBD) and lost the ability to resume meiosis.
  • Loss of Kiaa1429 led to abnormal RNA metabolism and altered expression of key oocyte factors.
  • Conditional Kiaa1429 depletion reduced oocyte m6A levels and affected alternative splicing of oogenesis-related genes.

Conclusions:

  • KIAA1429-mediated RNA metabolism is crucial for folliculogenesis and maintaining oocyte competence.
  • KIAA1429 plays a vital role in regulating RNA post-transcriptional modification essential for female reproductive success.

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