PABPN1 functions as a hub in the assembly of nuclear poly(A) domains that are essential for mouse oocyte development
Xing‐Xing Dai, Shuai‐Bo Pi, Long‐Wen Zhao, Yun‐Wen Wu, Jingling Shen, Songying Zhang, Qian‐Qian Sha, Heng‐Yu Fan
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, Pabpn1 fl/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.