ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development

Genome Biol. 2025 May 8;26(1):120. doi: 10.1186/s13059-025-03593-8.

Abstract

Background: During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability.

Results: Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3'-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs.

Conclusions: The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.

Keywords: Maternal-to-zygotic transition; Meiosis; Oocyte transcriptome; RNA polyadenylation; RNA-binding proteins.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Egg Proteins* / genetics
  • Egg Proteins* / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Mice
  • Oocytes* / growth & development
  • Oocytes* / metabolism
  • Oogenesis* / genetics
  • Polyadenylation*
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Messenger, Stored* / genetics
  • RNA, Messenger, Stored* / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Transcriptome

Substances

  • Egg Proteins
  • 3' Untranslated Regions
  • RNA, Messenger
  • RNA, Messenger, Stored
  • RNA-Binding Proteins