MOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Institute of Life Sciences, College of Life and Environmental Sciences, Wenzhou University, Wenzhou 325035, China.
Sci Adv. 2022 Oct 28;8(43):eabn9016. doi: 10.1126/sciadv.abn9016.
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. -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, 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.
生长中的卵母细胞储存大量的母体 mRNA，以支持随后的“母-合子过渡”过程。目前，尚不清楚生长中的卵母细胞在生理条件下如何储存和处理新转录的 mRNA。在这项研究中，我们报道了非膜结合区室、核多（A）域（NPAD），作为新转录 mRNA 的中心，在发育中的小鼠卵母细胞中。RNA 结合蛋白 PABPN1 通过其 N 端无序结构域和 RNA 识别基序，通过液-液相分离，促进 NPAD 的形成。-null 生长中的卵母细胞在体内不能正常形成 NPAD，并且卵母细胞生长相关转录物的稳定性和长 3'非翻译区异构体转录物的形成存在缺陷。最终， 小鼠表现出原发性卵巢功能不全的完全不育。这些结果表明，由 PABPN1-mRNA 的相分离特性形成的 NPAD 是新转录 mRNA 的中心，对卵母细胞的发育和雌性生殖至关重要。
