Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 22, 2023

In mammals, the production of mature oocytes necessitates rigorous regulation discontinuous meiotic cell-cycle progression at both transcriptional and post-transcriptional levels. However, factors underlying this sophisticated but explicit process remain largely unclear. Here we characterize function N-acetyltransferase 10 (Nat10), a writer for N4-acetylcytidine (ac4C) on RNA molecules, in mouse oocyte development. We provide genetic evidence that Nat10 is essential prophase I progression, growth maturation by sculpting maternal transcriptome through timely degradation poly(A) tail mRNAs. This achieved ac4C deposition key CCR4-NOT complex transcripts. Importantly, devise method examining length (PAT), termed Hairpin Adaptor-poly(A) (HA-PAT), which outperforms conventional methods terms cost, sensitivity, efficiency. summary, these findings unveils indispensable role

Language: Английский

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An extended wave of global mRNA deadenylation sets up a switch in translation regulation across the mammalian oocyte-to-embryo transition

Cell Reports, Journal Year: 2024, Volume and Issue: 43(2), P. 113710 - 113710

Published: Feb. 1, 2024

Without new transcription, gene expression across the oocyte-to-embryo transition (OET) relies instead on regulation of mRNA poly(A) tails to control translation. However, how tail dynamics shape translation OET in mammals remains unclear. We perform long-read RNA sequencing uncover lengths mouse and, incorporating published ribosome profiling data, provide an integrated, transcriptome-wide analysis and entire transition. extended wave global deadenylation during fertilization which short-tailed, oocyte-deposited mRNAs are translationally activated without polyadenylation through resistance deadenylation. Subsequently, embryo, readenylated translated a surge polyadenylation. further identify length at isoform level stage-specific enrichment sequence motifs among regulated transcripts. These data insight into mechanisms that orchestrate from oocyte embryo mammals.

Language: Английский

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Control of poly(A)-tail length and translation in vertebrate oocytes and early embryos

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(8), P. 1058 - 1074.e11

Published: March 8, 2024

During oocyte maturation and early embryogenesis, changes in mRNA poly(A)-tail lengths strongly influence translation, but how these tail-length are orchestrated has been unclear. Here, we performed translational profiling of reporter libraries (each with millions 3' UTR sequence variants) frog oocytes embryos fish embryos. Contrasting to previously proposed cytoplasmic polyadenylation elements (CPEs), found that a shorter element, UUUUA, together the signal (PAS), specify polyadenylation, identified contextual features modulate activity both elements. In maturing oocytes, this tail lengthening occurs against backdrop global deadenylation action C-rich tail-length-independent repression. embryos, becomes more permissive, additional waves stage-specific deadenylation. Together, findings largely explain complex tapestry observed development, strong evidence conservation mice humans.

Language: Английский

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核糖体介导的翻译调控与植物环境温度适应

Chinese Science Bulletin (Chinese Version), Journal Year: 2025, Volume and Issue: 70(7), P. 807 - 815

Published: Feb. 8, 2025

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Granulosa cell transcription is similarly impacted by superovulation and aging and predicts early embryonic trajectories

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 17, 2025

Abstract In vitro fertilization efficiency is limited in part because a fraction of retrieved oocytes fails to fertilize. Accurately evaluating their quality could significantly improve efficiency, which would require better understanding how maturation may be disrupted. Here, we quantitatively investigate the interplay between superovulation and aging mouse paired granulosa cells using newly adapted experimental methodology. We test hypothesis that disrupts oocyte maturation, revealing key intercellular communication pathways dysregulated at transcriptional level by forced hormonal stimulation. further demonstrate cell markers can prospectively predict an associated oocyte’s early developmental potential. By naturally ovulated old mice as non-stimulated reference, show dysregulate similar genes interact with each other. comparing human responses cells, find age-related dysregulation cycle are shared, though substantial divergence exists other pathways.

Language: Английский

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Isoform-resolved transcriptome of the human preimplantation embryo

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 30, 2023

Abstract Human preimplantation development involves extensive remodeling of RNA expression and splicing. However, its transcriptome has been compiled using short-read sequencing data, which fails to capture most full-length mRNAs. Here, we generate an isoform-resolved early human by performing long- on 73 embryos spanning the zygote blastocyst stages. We identify 110,212 unannotated isoforms transcribed from known genes, including highly conserved protein-coding loci key developmental regulators. further 17,964 5,239 are largely non-coding, primate-specific, associated with transposable elements. These widely supported integration published multi-omics datasets, single-cell 8CLC blastoid studies. Alternative splicing gene co-expression network analyses reveal that embryonic genome activation is disruption transient upregulation modules. Together, these findings show embryo far more complex than currently known, will act as a valuable resource empower future studies exploring development.

Language: Английский

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Germ cell-specific eIF4E1b regulates maternal mRNA translation to ensure zygotic genome activation

Genes & Development, Journal Year: 2023, Volume and Issue: 37(9-10), P. 418 - 431

Published: May 1, 2023

Translation of maternal mRNAs is detected before transcription zygotic genes and essential for mammalian embryo development. How certain are selected translation instead degradation how this burst affects genome activation remain unknown. Using gene-edited mice, we document that the oocyte-specific eukaryotic initiation factor 4E family member 1b (eIF4E1b) regulator mRNA expression ensures subsequent reprogramming genome. In oocytes, eIF4E1b binds to transcripts encoding machinery proteins, chromatin remodelers, factors promote their in zygotes protect them from degradation. The protein products thought establish an open landscape one-cell enable required cleavage stage Our results define a program rapid resetting epigenome regulated by provide new insights into maternal-to-zygotic transition.

Language: Английский

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The molecular mechanisms underpinning maternal mRNA dormancy

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(2), P. 861 - 871

Published: March 13, 2024

A large number of mRNAs maternal origin are produced during oogenesis and deposited in the oocyte. Since transcription stops at onset meiosis does not resume until later embryogenesis, only templates for protein synthesis this period. To ensure that a is made right place time, translation must be activated specific stage development. Here we summarize our current understanding sophisticated mechanisms contribute to temporal repression mRNAs, termed mRNA dormancy. We discuss level RNA itself, such as regulation polyadenine tail length modifications, well RNA-binding proteins, which often block assembly initiation complexes 5' end an or recruit subcellular compartments. also review microRNAs other repressing translation, ribosome Importantly, responsible dormancy oocyte-to-embryo transition relevant cellular quiescence biological contexts.

Language: Английский

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Stable maternal proteins underlie distinct transcriptome, translatome, and proteome reprogramming during mouse oocyte-to-embryo transition

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: July 13, 2023

Abstract Background The oocyte-to-embryo transition (OET) converts terminally differentiated gametes into a totipotent embryo and is critically controlled by maternal mRNAs proteins, while the genome silent until zygotic activation. How transcriptome, translatome, proteome are coordinated during this critical developmental window remains poorly understood. Results Utilizing highly sensitive quantitative mass spectrometry approach, we obtain high-quality data spanning seven mouse stages, from full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. Integrative analyses reveal distinct reprogramming compared that of transcriptome or translatome. FGO 8-cell proteomes dominated FGO-stockpiled translatome more dynamic. FGO-originated proteins frequently persist blastocyst corresponding transcripts already downregulated decayed. Improved concordance between protein translation transcription observed for genes starting upon meiotic resumption, as well those transcribed translated only in embryos. Concordance transcription/translation also with short half-lives. We built kinetic model predicts dynamics incorporating both initial abundance FGOs kinetics across stages. Conclusions Through integrative datasets generated ultrasensitive methods, our study reveals shows OET. propose remarkably stable oocyte-originated may help save resources accommodate demanding needs growing This will advance understanding mammalian OET fundamental principles governing gene expression.

Language: Английский

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Deadenylation kinetics of mixed poly(A) tails at single-nucleotide resolution

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(5), P. 826 - 834

Published: Feb. 19, 2024

Abstract Shortening of messenger RNA poly(A) tails, or deadenylation, is a rate-limiting step in mRNA decay and highly regulated during gene expression. The incorporation non-adenosines ‘mixed tailing’, has been observed vertebrates viruses. Here, to quantitate the effect mixed we mathematically modeled deadenylation reactions at single-nucleotide resolution using an vitro system reconstituted with complete human CCR4–NOT complex. Applying this model, assessed disrupting impact single guanosine, uridine cytosine be equivalent approximately 6, 8 11 adenosines, respectively. stalls 0, −1 −2 positions relative non-adenosine residue. CAF1 CCR4 enzyme subunits commonly prefer adenosine but exhibit distinct sequence selectivities stalling positions. Our study provides analytical framework monitor reveals molecular basis tail sequence-dependent regulation stability.

Language: Английский

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