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

First Author  Dai XX Year  2022
Journal  Sci Adv Volume  8
Issue  43 Pages  eabn9016
PubMed ID  36306357 Mgi Jnum  J:331065
Mgi Id  MGI:7383987 Doi  10.1126/sciadv.abn9016
Citation  Dai XX, et al. (2022) PABPN1 functions as a hub in the assembly of nuclear poly(A) domains that are essential for mouse oocyte development. Sci Adv 8(43):eabn9016
abstractText  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. <i>Pabpn1</i>-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, <i>Pabpn1<sup>fl/fl</sup>;Gdf9-Cre</i> 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.
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