PABPN1 functions as a hub in the assembly of nuclear poly(A) domains that are essential for mouse oocyte development

Sci Adv. 2022 Oct 28;8(43):eabn9016. doi: 10.1126/sciadv.abn9016. Epub 2022 Oct 28.

Abstract

Growing oocytes store a large amount of maternal mRNA to support the subsequent "maternal-zygotic transition" process. At present, it is not clear how the growing oocytes store and process the newly transcribed mRNA under physiological conditions. In this study, we report non-membrane-bound compartments, nuclear poly(A) domains (NPADs), as the hub for newly transcribed mRNA, in developing mouse oocytes. The RNA binding protein PABPN1 promotes the formation of NPAD through its N-terminal disordered domain and RNA-recognized motif by means of liquid phase separation. Pabpn1-null growing oocytes cannot form NPAD normally in vivo and have defects in stability of oocyte growing-related transcripts and formation of long 3' untranslated region isoform transcripts. Ultimately, Pabpn1fl/fl;Gdf9-Cre mice are completely sterile with primary ovarian insufficiency. These results demonstrate that NPAD formed by the phase separation properties of PABPN1-mRNA are the hub of the newly transcribed mRNA and essential for the development of oocytes and female reproduction.

MeSH terms

  • Animals
  • Cell Nucleus* / metabolism
  • Female
  • Mice
  • Oocytes / metabolism
  • Poly A* / genetics
  • Poly A* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Poly A
  • RNA, Messenger
  • RNA-Binding Proteins
  • PABPN1 protein, mouse