Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment

• Published in: Science (American Association for the Advancement of Science) Vol. 378; no. 6617; p. eabq4835
• Main Authors: Cheng, Shiya, Altmeppen, Gerrit, So, Chun, Welp, Luisa M., Penir, Sarah, Ruhwedel, Torben, Menelaou, Katerina, Harasimov, Katarina, Stützer, Alexandra, Blayney, Martyn, Elder, Kay, Möbius, Wiebke, Urlaub, Henning, Schuh, Melina
• Format: Journal Article
• Language: English
• Published: Washington The American Association for the Advancement of Science 21.10.2022
• Subjects: Assembly; Chromosomes; Clustering; Coalescence; Compartments; Cytokinesis; Cytoplasm; Degradation; Developmental stages; Eggs; Embryogenesis; Embryonic growth stage; Embryos; Endoplasmic reticulum; Endosomes; Fertility; Fertilization; Fluorescence in situ hybridization; Gametocytes; Genomes; Golgi apparatus; Granular materials; Hydrogels; Localization; Lysosomes; Mammals; Maturation; Meiosis; Membrane potential; Membranes; Mitochondria; Nucleic acids; Oocytes; Phase separation; Protein turnover; Proteins; Ribonucleic acid; RNA; RNA-binding protein; Storage; Transcription
• ISSN: 0036-8075; 1095-9203; 1095-9203
• 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. Mammalian oocytes stop transcribing DNA into messenger RNA (mRNA) during the final stages of their development. The oocyte’s meiotic divisions and early embryo development occur in the absence of transcription and rely instead on maternal mRNAs that are stored in the oocyte. However, where and how mammalian oocytes store mRNAs has remained elusive. Cheng et al . discovered that mammalian oocytes, including those in humans, store maternal mRNAs around the mitochondria in a membraneless compartment with hydrogel-like properties. The RNA-binding protein ZAR1 drives the assembly of this compartment, which clusters the mitochondria and protects the mRNAs against degradation. —SMH A membraneless compartment clusters mitochondria and stores maternal mRNAs in oocytes of various mammalian species.