bims-cebooc 2024-10-20 papers

Issue of 2024‒10‒20
six papers selected by
Gabriele Zaffagnini, Centre for Genomic Regulation

Nat Cell Biol. 2024 Oct 16.

Ex vivo imaging reveals the spatiotemporal control of ovulation.

Christopher Thomas, Tabea Lilian Marx, Sarah Mae Penir, Melina Schuh.

During ovulation, an egg is released from an ovarian follicle, ready for fertilization. Ovulation occurs inside the body, impeding direct studies of its progression. Therefore, the exact mechanisms that control ovulation have remained unclear. Here we devised live imaging methods to study the entire process of ovulation in isolated mouse ovarian follicles. We show that ovulation proceeds through three distinct phases, follicle expansion (I), contraction (II) and rupture (III), culminating in the release of the egg. Follicle expansion is driven by hyaluronic acid secretion and an osmotic gradient-directed fluid influx into the follicle. Then, smooth muscle cells in the outer follicle drive follicle contraction. Follicle rupture begins with stigma formation, followed by the exit of follicular fluid and cumulus cells and the rapid release of the egg. These results establish a mechanistic framework for ovulation, a process of fundamental importance for reproduction.

DOI: https://doi.org/10.1038/s41556-024-01524-6

Mol Cell Proteomics. 2024 Oct 14. pii: S1535-9476(24)00152-X. [Epub ahead of print] 100862

Integrative omics reveals the metabolic patterns during oocyte growth.

Xiang Zhang, Juan Ge, Yue Wang, Minjian Chen, Xuejiang Guo, Shuai Zhu, Hui Wang, Qiang Wang.

Well-controlled metabolism is associated with high quality of oocytes and optimal development of a healthy embryo. However, the metabolic framework that controls mammalian oocyte growth remains unknown. In the present study, we comprehensively depict the temporal metabolic dynamics of mouse oocytes during in vivo growth through the integrated analysis of metabolomics and proteomics. A number of novel metabolic features are discovered during this process. Of note, glycolysis is enhanced and oxidative phosphorylation capacity is reduced in the growing oocytes, presenting a Warburg-like metabolic program. For the nucleotide biosynthesis, the salvage pathway is markedly activated during oocyte growth, whereas the de novo pathway is evidently suppressed. Fatty acid synthesis and channeling into phosphoinositides are specifically elevated in oocytes accompanying primordial follicle activation; nevertheless, fatty acid oxidation is reduced in these oocytes simultaneously. Our data establish the metabolic landscape during in vivo oocyte growth and serve as a broad resource for probing mammalian oocyte metabolism.

Keywords: Metabolism; follicle; oocyte; proteomics; reproduction

DOI: https://doi.org/10.1016/j.mcpro.2024.100862

Nat Commun. 2024 Oct 15. 15(1): 8887

The subcortical maternal complex modulates the cell cycle during early mammalian embryogenesis via 14-3-3.

The subcortical maternal complex (SCMC) is essential for safeguarding female fertility in mammals. Assembled in oocytes, the SCMC maintains the cleavage of early embryos, but the underlying mechanism remains unclear. Here, we report that 14-3-3, a multifunctional protein, is a component of the SCMC. By resolving the structure of the 14-3-3-containing SCMC, we discover that phosphorylation of TLE6 contributes to the recruitment of 14-3-3. Mechanistically, during maternal-to-embryo transition, the SCMC stabilizes 14-3-3 protein and contributes to the proper control of CDC25B, thus ensuring the activation of the maturation-promoting factor and mitotic entry in mouse zygotes. Notably, the SCMC establishes a conserved molecular link with 14-3-3 and CDC25B in human oocytes/embryos. This study discloses the molecular mechanism through which the SCMC regulates the cell cycle in early embryos and elucidates the function of the SCMC in mammalian early embryogenesis.

DOI: https://doi.org/10.1038/s41467-024-53277-3

Aging Cell. 2024 Oct 15. e14376

The N6-methyladenosine landscape of ovarian development and aging highlights the regulation by RNA stability and chromatin state.

Xiujuan Hu, Jiafeng Lu, Chenyue Ding, Jincheng Li, Qinyan Zou, Wenjuan Xia, Chunfeng Qian, Hong Li, Boxian Huang.

The versatile epigenetic modification known as N6-methyladenosine (m6A) has been demonstrated to be pivotal in numerous physiological and pathological contexts. Nonetheless, the precise regulatory mechanisms linking m6A to histone modifications and the involvement of transposable elements (TEs) in ovarian development and aging are still not completely understood. First, we discovered that m6A modifications are highly expressed during ovarian aging (OA), with significant contributions from decreased m6A demethylase FTO and overexpressed m6A methyltransferase METTL16. Then, using FTO knockout mouse model and KGN cell line, we also observed that FTO deletion and METTL16 overexpression significantly increased m6A levels. This led to the downregulation of the methyltransferase SUV39H1, resulting in reduced H3K9me3 expression. The downregulation of SUV39H1 and H3K9me3 primarily activated LTR7 and LTR12, subsequently activating ERV1. This resulted in a decrease in cell proliferation, while the levels of apoptosis, cellular aging markers, and autophagy markers significantly increased in OA. In summary, our study offers intriguing insights into the role of m6A in regulating DNA epigenetics, including H3K9me3 and TEs, as well as autophagy, thereby accelerating OA.

Keywords: FTO; H3K9me3; METTL16; N6‐methyladenosine; SUV39H1; autophagy; endogenous retroviruses; ovarian aging

DOI: https://doi.org/10.1111/acel.14376

Curr Biol. 2024 Oct 04. pii: S0960-9822(24)01245-4. [Epub ahead of print]

Length-sensitive partitioning of Caenorhabditiselegans meiotic chromosomes responds to proximity and number of crossover sites.

Carlos M Rodriguez-Reza, Aya Sato-Carlton, Peter M Carlton.

Sensing and control of size are critical for cellular function and survival. A striking example of size sensing occurs during meiosis in the nematode Caenorhabditis elegans. C. elegans chromosomes compare the lengths of the two chromosome "arms" demarcated by the position of their single off-center crossover, and they differentially modify these arms to ensure that sister chromatid cohesion is lost specifically on the shorter arm in the first meiotic division, while the longer arm maintains cohesion until the second division. While many of the downstream steps leading to cohesion loss have been characterized, the length-sensing process itself remains poorly understood. Here, we have used cytological visualization of short and long chromosome arms, combined with quantitative microscopy, live imaging, and simulations, to investigate the principles underlying length-sensitive chromosome partitioning. By quantitatively analyzing short-arm designation patterns on fusion chromosomes carrying multiple crossovers, we develop a model in which a short-arm-determining factor originates at crossover designation sites, diffuses within the synaptonemal complex, and accumulates within crossover-bounded chromosome segments. We demonstrate experimental support for a critical assumption of this model: that crossovers act as boundaries to diffusion within the synaptonemal complex. Further, we develop a discrete simulation based on our results that recapitulates a wide variety of observed partitioning outcomes in both wild-type and previously reported mutants. Our results suggest that the concentration of a diffusible factor is used as a proxy for chromosome length, enabling the correct designation of short and long arms and proper segregation of chromosomes.

Keywords: C. elegans; SYP-1; chromosome segregation; holocentric chromosomes; length sensing; live imaging; meiosis; photoconversion; super-resolution imaging; synaptonemal complex

DOI: https://doi.org/10.1016/j.cub.2024.09.034

EMBO J. 2024 Oct 14.

The dynamics and functional impact of tRNA repertoires during early embryogenesis in zebrafish.

Madalena M Reimão-Pinto, Andrew Behrens, Sergio Forcelloni, Klemens Fröhlich, Selay Kaya, Danny D Nedialkova.

Embryogenesis entails dramatic shifts in mRNA translation and turnover that reprogram gene expression during cellular proliferation and differentiation. Codon identity modulates mRNA stability during early vertebrate embryogenesis, but how the composition of tRNA pools is matched to translational demand is unknown. By quantitative profiling of tRNA repertoires in zebrafish embryos during the maternal-to-zygotic transition, we show that zygotic tRNA repertoires are established after the onset of gastrulation, succeeding the major wave of zygotic mRNA transcription. Maternal and zygotic tRNA pools are distinct, but their reprogramming does not result in a better match to the codon content of the zygotic transcriptome. Instead, we find that an increase in global translation at gastrulation sensitizes decoding rates to tRNA supply, thus destabilizing maternal mRNAs enriched in slowly translated codons. Translational activation and zygotic tRNA expression temporally coincide with an increase of TORC1 activity at gastrulation, which phosphorylates and inactivates the RNA polymerase III repressor Maf1a/b. Our data indicate that a switch in global translation, rather than tRNA reprogramming, determines the onset of codon-dependent maternal mRNA decay during zebrafish embryogenesis.

Keywords: Maternal-to-zygotic Transition; TORC1; Translation Regulation; Zebrafish; tRNA

DOI: https://doi.org/10.1038/s44318-024-00265-4