Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Science. 2022 Oct 21;378(6617):eabq4835. doi: 10.1126/science.abq4835.
Full-grown oocytes are transcriptionally silent and must stably maintain the messenger RNAs (mRNAs) needed for oocyte meiotic maturation and early embryonic development. However, where and how mammalian oocytes store maternal mRNAs is unclear. Here, we report that mammalian oocytes accumulate mRNAs in a mitochondria-associated ribonucleoprotein domain (MARDO). MARDO assembly around mitochondria was promoted by the RNA-binding protein ZAR1 and directed by an increase in mitochondrial membrane potential during oocyte growth. MARDO foci coalesced into hydrogel-like matrices that clustered mitochondria. Maternal mRNAs stored in the MARDO were translationally repressed. Loss of ZAR1 disrupted the MARDO, dispersed mitochondria, and caused a premature loss of MARDO-localized mRNAs. Thus, a mitochondria-associated membraneless compartment controls mitochondrial distribution and regulates maternal mRNA storage, translation, and decay to ensure fertility in mammals.
成熟的卵母细胞转录沉默,必须稳定地维持卵母细胞减数分裂成熟和早期胚胎发育所需的信使 RNA(mRNA)。然而,哺乳动物卵母细胞在哪里以及如何储存母体 mRNA 尚不清楚。在这里,我们报告说,哺乳动物卵母细胞在与线粒体相关的核糖核蛋白域(MARDO)中积累 mRNA。MARDO 围绕线粒体的组装是由 RNA 结合蛋白 ZAR1 促进的,并且在卵母细胞生长过程中线粒体膜电位的增加所指导。MARDO 焦点凝聚成凝胶样基质,使线粒体聚集。储存在 MARDO 中的母体 mRNA 被翻译抑制。ZAR1 的缺失破坏了 MARDO,使线粒体分散,并导致 MARDO 定位的 mRNA 过早丢失。因此,一种与线粒体相关的无膜隔室控制着线粒体的分布,并调节母体 mRNA 的储存、翻译和降解,以确保哺乳动物的生育能力。