PGC7 regulates maternal mRNA translation via AKT1-YBX1 interactions in mouse oocytes

Cell Commun Signal. 2024 Dec 18;22(1):604. doi: 10.1186/s12964-024-01976-1.

Abstract

Timely and accurate translation of maternal mRNA is essential for oocyte maturation and early embryonic development. Previous studies have highlighted the importance of Primordial Germ cell 7 (PGC7) as a maternal factor in maintaining DNA methylation of maternally imprinted loci in zygotes. However, it is still unknown whether PGC7 is involved in the regulation of Maternal mRNA Translation. In this study, we have identified that PGC7-AKT1-YBX1 axis is involved in promoting the translation of maternal mRNAs. PGC7 not only sustains AKT1 activity by counteracting PP2A dephosphorylation and facilitating PDK1-AKT1 binding but also assists AKT1 in phosphorylating the translation inhibitor YBX1. In the absence of PGC7, despite increased PIK3CA expression and AKT1 phosphorylation, AKT1 is unable to phosphorylate YBX1. PGC7 facilitates the interaction between AKT1 and YBX1, enhancing YBX1-Serine 100 phosphorylation, which leads to YBX1 dissociation from eIF4E, thereby activating the translation of maternal Cyclin B1 and YAP1. The findings demonstrate the indispensability of PGC7 for translation activation in mammalian oocytes and provide a potential network regulated by PGC7 in early oogenesis.

Keywords: AKT1; Maternal mRNA translation; Oocyte; PGC7; YBX1.

MeSH terms

  • Animals
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Eukaryotic Initiation Factor-4E / genetics
  • Eukaryotic Initiation Factor-4E / metabolism
  • Female
  • Mice
  • Oocytes* / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Messenger, Stored / genetics
  • RNA, Messenger, Stored / metabolism
  • Transcription Factors
  • Y-Box-Binding Protein 1* / genetics
  • Y-Box-Binding Protein 1* / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Y-Box-Binding Protein 1
  • YB-1 protein, mouse
  • Akt1 protein, mouse
  • RNA, Messenger, Stored
  • Eukaryotic Initiation Factor-4E
  • Cyclin B1
  • RNA, Messenger
  • Transcription Factors