The APC/CFZY-1/Cdc20 complex coordinates with OMA-1 to regulate the oocyte-to-embryo transition in C. elegans
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PROVIDER: PRJNA750733 | ENA |
REPOSITORIES: ENA
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Project description:During oocyte maturation and the oocyte-to-embryo transition, key developmental regulators such as RNA-binding proteins coordinate translation of particular mRNAs and related developmental processes by binding to their cognate maternal mRNAs. In the nematode C. elegans, these processes are regulated by a set of CCCH zinc finger proteins. OMA-1 and OMA-2 are two functionally redundant CCCH zinc finger proteins that turnover rapidly during the first embryonic cell division. These turnovers are required for proper transition from oogenesis to embryogenesis. A gain-of-function mutant of OMA-1, oma-1(zu405), stabilizes and delays degradation of OMA-1, resulting in delayed turnover and mis-segregation of other cell fate determinants, which eventually causes embryonic lethality. We performed a large-scale forward genetic screen to identify suppressors of the oma-1(zu405) mutant. We show here that multiple alleles affecting functions of various APC/C subunits, including MAT-1, MAT-2, MAT-3, EMB-30, and FZY-1, suppress the gain-of-function mutant of OMA-1. Mutations in APC/C genes prevent OMA-1 enrichment in P granules and correct delayed degradation of downstream cell fate determinants including PIE-1, POS-1, MEX-3, and MEG-1. Transcriptome analysis also suggested that overall transcription in early embryos occurred after introducing mutations in APC/C genes into the oma-1(zu405) mutant. We demonstrated that only the activator FZY-1, but not FZR-1, is incorporated in the APC/C complex to regulate the oocyte-to-embryo transition. Our findings suggested a genetic relationship linking the APC/C complex and OMA-1, and support a model in which the APC/C complex promotes P granule accumulation and modifies RNA binding of OMA-1 to regulate the oocyte-to-embryo transition process.
2021-10-02 | GSE181115 | GEO
Project description:An extended meiotic prophase is a hallmark of oogenesis. Hormonal signaling activates the CDK1/cyclin B kinase to promote oocyte meiotic maturation, which involves nuclear and cytoplasmic events. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation. Cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is poorly understood. In the nematode Caenorhabditis elegans, sperm release the major sperm protein (MSP) hormone to promote oocyte growth and meiotic maturation. Large translational regulatory ribonucleoprotein (RNP) complexes containing the RNA-binding proteins OMA-1, OMA-2, and LIN-41 regulate meiotic maturation downstream of MSP signaling. To understand the control of translation during meiotic maturation, we purified LIN-41-containing RNPs and characterized their protein and RNA components. Protein constituents of LIN-41 RNPs include essential RNA-binding proteins, the GLD-2 cytoplasmic poly(A) polymerase, the CCR4-NOT deadenylase complex, and translation initiation factors. RNA sequencing defined mRNAs associated with both LIN-41 and OMA-1, as well as sets of mRNAs associated with either LIN-41 or OMA-1. Genetic and genomic evidence suggests that GLD-2, which is a component of LIN-41 RNPs, stimulates the efficient translation of many LIN-41-associated transcripts. We analyzed the translational regulation of two transcripts specifically associated with LIN-41 that encode the RNA regulators SPN-4 and MEG-1. We found that LIN-41 represses translation of spn-4 and meg-1, whereas OMA-1 and OMA-2 promote their expression. Upon their synthesis, SPN-4 and MEG-1 assemble into LIN-41 RNPs prior to their functions in the embryo. This study defines a translational repression-to-activation switch as a key element of cytoplasmic maturation.
2017-06-02 | GSE98130 | GEO
Project description:An extended meiotic prophase is a hallmark of oogenesis. Hormonal signaling activates the CDK1/cyclin B kinase to promote oocyte meiotic maturation, which involves nuclear and cytoplasmic events. Nuclear maturation encompasses nuclear envelope breakdown, meiotic spindle assembly, and chromosome segregation. Cytoplasmic maturation involves major changes in oocyte protein translation and cytoplasmic organelles and is poorly understood. In the nematode Caenorhabditis elegans, sperm release the major sperm protein (MSP) hormone to promote oocyte growth and meiotic maturation. Large translational regulatory ribonucleoprotein (RNP) complexes containing the RNA-binding proteins OMA-1, OMA-2, and LIN-41 regulate meiotic maturation downstream of MSP signaling. To understand the control of translation during meiotic maturation, we purified LIN-41-containing RNPs and characterized their protein and RNA components. Protein constituents of LIN-41 RNPs include essential RNA-binding proteins, the GLD-2 cytoplasmic poly(A) polymerase, the CCR4-NOT deadenylase complex, and translation initiation factors. RNA sequencing defined mRNAs associated with both LIN-41 and OMA-1, as well as sets of mRNAs associated with either LIN-41 or OMA-1. Genetic and genomic evidence suggests that GLD-2, which is a component of LIN-41 RNPs, stimulates the efficient translation of many LIN-41-associated transcripts. We analyzed the translational regulation of two transcripts specifically associated with LIN-41 that encode the RNA regulators SPN-4 and MEG-1. We found that LIN-41 represses translation of spn-4 and meg-1, whereas OMA-1 and OMA-2 promote their expression. Upon their synthesis, SPN-4 and MEG-1 assemble into LIN-41 RNPs prior to their functions in the embryo. This study defines a translational repression-to-activation switch as a key element of cytoplasmic maturation.
2017-06-16 | PXD006726 | Pride
Project description:Post-transcriptional mechanisms are crucial for the regulation of gene expression. These mechanisms are particularly important during rapid developmental transitions such as the oocyte-to-embryo transition, which is characterized by dramatic changes to the developmental program in the absence of nuclear transcription. Under these conditions, changes to the RNA content are solely dependent on RNA degradation. Although several mechanisms that promote RNA decay during embryogenesis have been identified, it remains unclear which cellular machineries contribute to remodeling the maternal transcriptome during the oocyte-to-embryo transition. Here, we focused on the auxiliary 3’-to-5’ degradation factor Ski7 in zebrafish as its mRNA peaks during this time frame. Homozygous ski7 mutant fish were viable and developed into morphologically normal adults, yet they had decreased fertility. Consistent with the idea that Ski7 participates in remodeling the transcriptome during the oocyte-to-embryo transition, transcriptome profiling identified stage-specific mRNA targets of Ski7. Genes upregulated in ski7 mutants were generally lowly expressed in wild type, suggesting that Ski7 maintains low transcript levels for this subset of genes. GO enrichment analyses of genes mis-regulated in ski7 mutants implicated Ski7 in the regulation of redox processes. This was confirmed experimentally by an increased resistance of ski7 mutant embryos to reductive stress. Overall, our results provide first insights into the physiological role of vertebrate Ski7 as an important post-transcriptional regulator during the oocyte-to-embryo transition.
2021-02-12 | GSE147112 | GEO
Project description:The oocyte-to-embryo transition converts terminally differentiated gametes into a totipotent embryo. Fertilized embryos undergo the resetting of the transcriptional program as the zygotic genome is activated from a silenced state started from the late-stage oocyte. How transcriptome, translatome, and proteome interplay in this critical developmental window remains poorly understood. Utilizing a highly sensitive mass spectrometry, we obtained high-quality proteome landscapes including nearly 6,000 genes spanning 10 stages, from the mouse full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. By integrative analysis with corresponding transcriptomes and translatomes, we found transcription and translation levels can not reflect protein abundance in most cases. From FGOs to the 4-cell embryos, the proteomes are predominated by FGO-produced proteins, while the transcriptome and the translatome are much more dynamic. FGO-originated proteins frequently persist in embryos after the corresponding transcripts are already downregulated or decayed. Improved concordance between protein and RNA is observed for genes starting translation only upon meiotic resumption or transcribed only in embryos, although the detected protein dynamics often lag behind transcription and translation. Concordance between protein and transcription/translation is associated with protein half-lives. Finally, a kinetic model well predicts protein dynamics when incorporating both the initial protein abundance in FGO and translation kinetics across developmental stages. In sum, our study reveals multilayer control of gene expression during oocyte maturation and embryogenesis.
2023-06-27 | PXD035696 | Pride
Project description:The oocyte-to-embryo transition (OET) occurs in the absence of new transcription and relies on post-transcriptional gene regulation, including translational control by mRNA poly(A) tail regulation, where cytoplasmic polyadenylation activates translation and deadenylation leads to translational repression and decay. However, how the transcriptome-wide landscape of mRNA poly(A) tails shapes translation across the OET in mammals remains unknown. Here, we performed long-read RNA sequencing to uncover poly(A) tail lengths and mRNA abundance transcriptome-wide in mice across five stages of development from oocyte to embryo. Integrating these data with recently published ribosome profiling data, we demonstrate that poly(A) tail length is coupled to translational efficiency across the entire OET. We uncover an extended wave of global deadenylation during fertilization, which sets up a switch in translation control between the oocyte and embryo. In the oocyte, short-tailed maternal mRNAs that resist deadenylation in the oocyte are translationally activated, whereas large groups of mRNAs deadenylated without decay in the oocyte are later readenylated to drive translation activation in the early embryo. Our findings provide an important resource and insight into the mechanisms by which cytoplasmic polyadenylation and deadenylation dynamically shape poly(A) tail length in a stage-specific manner to orchestrate development from oocyte to embryo in mammals.
2024-03-14 | GSE228001 | GEO
Project description:The complex cellular events that occur in response to fertilization are essential for mediating the oocyte-to-embryo transition. Here, we describe a comprehensive small molecule screen focused on identifying compounds that affect the oocyte-to-embryo transition in C. elegans. We identify a single novel compound that disrupts early embryogenesis with remarkable stage- and species-specificity. The compound, named C22, primarily impairs eggshell integrity, leading to osmotic sensitivity and embryonic lethality. We show that this phenotype is dependent upon the upregulation of the LET-607/CREBH transcription factor. We then demonstrate that LET-607 candidate gene targets primarily encode factors involved in diverse aspects of protein trafficking. Together, our data suggest that in the presence of C22, one or more key components of the eggshell are inappropriately processed, leading to permeable, inviable embryos. The remarkable specificity and reversibility of this compound will facilitate further investigation into the role and regulation of protein trafficking in the early embryo, as well as serve as a tool for manipulating the life cycle for other studies such as aging.
2016-12-06 | GSE84419 | GEO
Project description:Translation is critical for development as transcription in the oocyte and early embryo is silenced. To illustrate the translational changes during meiosis and consecutive two mitoses of the oocyte and early embryo, we performed a genome-wide translatome analysis. Acquired data showed significant and uniform activation of key translational initiation and elongation axes specific to M-phases. Although global protein synthesis decreases in M-phases, translation initiation and elongation activity increases in a uniformly fluctuating manner, leading to qualitative changes in translation regulation via the mTOR1/4F/eEF2 axis. Overall, we have uncovered a highly dynamic and oscillatory pattern of translational reprogramming that contributes to the translational regulation of specific mRNAs with different modes of polysomal occupancy/translation that are important for oocyte and embryo developmental competence. Our results provide new insights into the regulation of gene expression during oocyte meiosis as well as the first two embryonic mitoses and show, how temporal translation can be optimized. This study is the first step towards a comprehensive analysis of the molecular mechanisms that not only control translation during early development, but also regulate translation-related networks employed in the oocyte-to-embryo transition and embryonic genome activation.
2023-05-29 | GSE230016 | GEO
Project description:Oocyte-to-embryo transition plays a critical role in oocyte maturation and embryogenesis. It is a highly regulated process in part due to a transcription silenced period followed by zygotic genome activation. How transcriptome, translatome, and proteome interplay in this critical developmental window remains poorly understood. Utilizing a highly sensitive mass spectrometry, we obtained a high-quality proteome landscape spanning 10 stages, from the mouse full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. By integrative analysis with corresponding transcriptome and translatome, we found transcription and translation levels can not reflect protein abundance in most cases. From FGO to 4-cell embryos, proteomes are predominated by FGO-produced proteins, while the transcriptome and translatome are much more dynamic. FGO inherited proteins frequently persist after the corresponding transcripts are already downregulated or decayed. Improved concordance between protein and RNA is observed for genes starting translation only upon meiotic resumption (OET upregulated) or transcribed only in embryos, although the detected protein dynamics often lag behind transcription and translation. Concordance between protein and transcription/tranlation is associated with protein half-lives. Finally, a kinetic model well predicts protein dynamics when incorporating both the initial protein abundance in FGO and translation kinetics across developmental stages. In sum, our study reveals multilayer control of gene expression during oocyte maturation and embryogenesis.
2023-06-06 | GSE209648 | GEO
Project description:Zebrafish Ski7 tunes RNA levels during the oocyte-to-embryo transition
| PRJNA613025 | ENA