A story of birth and death: mRNA translation and clearance at the onset of maternal-to-zygotic transition in mammals†

Abstract In mammals, maternal-to-zygotic transition (MZT), or oocyte-to-embryo transition, begins with oocyte meiotic resumption due to the sequential translational activation and destabilization of dormant maternal transcripts stored in the ooplasm. It then continues with the elimination of maternal transcripts during oocyte maturation and fertilization and ends with the full transcriptional activation of the zygotic genome during embryonic development. A hallmark of MZT in mammals is its reliance on translation and the utilization of stored RNAs and proteins, rather than de novo transcription of genes, to sustain meiotic maturation and early development. Impaired maternal mRNA clearance at the onset of MZT prevents zygotic genome activation and causes early arrest of developing embryos. In this review, we discuss recent advances in our knowledge of the mechanisms whereby mRNA translation and degradation are controlled by cytoplasmic polyadenylation and deadenylation which set up the competence of maturing oocyte to accomplish MZT. The emphasis of this review is on the mouse as a model organism for mammals and BTG4 as a licensing factor of MZT under the translational control of the MAPK cascade.

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Characterization of zygotic genome activation-dependent maternal mRNA clearance in mouse

Nucleic Acids Research ◽

10.1093/nar/gkz1111 ◽

2019 ◽

Vol 48 (2) ◽

pp. 879-894 ◽

Cited By ~ 5

Author(s):

Qian-Qian Sha ◽

Ye-Zhang Zhu ◽

Sen Li ◽

Yu Jiang ◽

Lu Chen ◽

...

Keyword(s):

De Novo ◽

Mouse Embryos ◽

Developmental Competence ◽

Preimplantation Embryos ◽

Zygotic Genome Activation ◽

Cell Stage ◽

Maternal Mrna ◽

Maternal Transcripts ◽

Genome Activation ◽

Zygotic Genome

Abstract An important event of the maternal-to-zygotic transition (MZT) in animal embryos is the elimination of a subset of the maternal transcripts that accumulated during oogenesis. In both invertebrates and vertebrates, a maternally encoded mRNA decay pathway (M-decay) acts before zygotic genome activation (ZGA) while a second pathway, which requires zygotic transcription, subsequently clears additional mRNAs (Z-decay). To date the mechanisms that activate the Z-decay pathway in mammalian early embryos have not been investigated. Here, we identify murine maternal transcripts that are degraded after ZGA and show that inhibition of de novo transcription stabilizes these mRNAs in mouse embryos. We show that YAP1-TEAD4 transcription factor-mediated transcription is essential for Z-decay in mouse embryos and that TEAD4-triggered zygotic expression of terminal uridylyltransferases TUT4 and TUT7 and mRNA 3′-oligouridylation direct Z-decay. Components of the M-decay pathway, including BTG4 and the CCR4-NOT deadenylase, continue to function in Z-decay but require reinforcement from the zygotic factors for timely removal of maternal mRNAs. A long 3′-UTR and active translation confer resistance of Z-decay transcripts to M-decay during oocyte meiotic maturation. The Z-decay pathway is required for mouse embryo development beyond the four-cell stage and contributes to the developmental competence of preimplantation embryos.

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Developmental series of gene expression clarifies maternal mRNA provisioning and maternal-to-zygotic transition in a reef-building coral

BMC Genomics ◽

10.1186/s12864-021-08114-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Erin Chille ◽

Emma Strand ◽

Mayaan Neder ◽

Valeria Schmidt ◽

Madeleine Sherman ◽

...

Keyword(s):

Gene Expression ◽

Cell Division ◽

Transcriptional Repression ◽

Developmental Stages ◽

Functional Enrichment ◽

Peptide Transport ◽

Maternal Mrna ◽

Maternal To Zygotic Transition ◽

Maternal Transcripts ◽

Baseline Information

Abstract Background Maternal mRNA provisioning of oocytes regulates early embryogenesis. Maternal transcripts are degraded as zygotic genome activation (ZGA) intensifies, a phenomenon known as the maternal-to-zygotic transition (MZT). Here, we examine gene expression over nine developmental stages in the Pacific rice coral, Montipora capitata, from eggs and embryos at 1, 4, 9, 14, 22, and 36 h-post-fertilization (hpf), as well as swimming larvae (9d), and adult colonies. Results Weighted Gene Coexpression Network Analysis revealed four expression peaks, identifying the maternal complement, two waves of the MZT, and adult expression. Gene ontology enrichment revealed maternal mRNAs are dominated by cell division, methylation, biosynthesis, metabolism, and protein/RNA processing and transport functions. The first MZT wave occurs from ~4-14 hpf and is enriched in terms related to biosynthesis, methylation, cell division, and transcription. In contrast, functional enrichment in the second MZT wave, or ZGA, from 22 hpf-9dpf, includes ion/peptide transport and cell signaling. Finally, adult expression is enriched for functions related to signaling, metabolism, and ion/peptide transport. Our proposed MZT timing is further supported by expression of enzymes involved in zygotic transcriptional repression (Kaiso) and activation (Sox2), which peak at 14 hpf and 22 hpf, respectively. Further, DNA methylation writing (DNMT3a) and removing (TET1) enzymes peak and remain stable past ~4 hpf, suggesting that methylome programming occurs before 4 hpf. Conclusions Our high-resolution insight into the coral maternal mRNA and MZT provides essential baseline information to understand parental carryover effects and the sensitivity of developmental success under increasing environmental stress.

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Transcriptional Activation of Arabidopsis Zygotes Is Required for Initial Cell Divisions

Scientific Reports ◽

10.1038/s41598-019-53704-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 15

Author(s):

Ping Kao ◽

Michael D. Nodine

Keyword(s):

Transcriptional Activation ◽

Gene Products ◽

Zygotic Genome Activation ◽

Microscopy Technique ◽

Early Embryos ◽

Maternal To Zygotic Transition ◽

Parental Gene ◽

Active Transcription ◽

Genome Activation ◽

Zygotic Genome

AbstractCommonly referred to as the maternal-to-zygotic transition, the shift of developmental control from maternal-to-zygotic genomes is a key event during animal and plant embryogenesis. Together with the degradation of parental gene products, the increased transcriptional activities of the zygotic genome remodels the early embryonic transcriptome during this transition. Although evidence from multiple flowering plants suggests that zygotes become transcriptionally active soon after fertilization, the timing and developmental requirements of zygotic genome activation in Arabidopsis thaliana (Arabidopsis) remained a matter of debate until recently. In this report, we optimized an expansion microscopy technique for robust immunostaining of Arabidopsis ovules and seeds. This enabled the detection of marks indicative of active transcription in zygotes before the first cell division. Moreover, we employed a live-imaging culture system together with transcriptional inhibitors to demonstrate that such active transcription is physiologically required in zygotes and early embryos. Our results indicate that zygotic genome activation occurs soon after fertilization and is required for the initial zygotic divisions in Arabidopsis.

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Positive and negative cis-regulatory elements directing postfertilization maternal mRNA translational control in mouse embryos

AJP Cell Physiology ◽

10.1152/ajpcell.00166.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. C818-C827 ◽

Cited By ~ 10

Author(s):

Santhi Potireddy ◽

Uros Midic ◽

Cheng-Guang Liang ◽

Zoran Obradovic ◽

Keith E. Latham

Keyword(s):

Secondary Structure ◽

Translational Control ◽

Bioinformatics Analysis ◽

Mrna Translation ◽

Regulatory Elements ◽

Regulatory Mechanisms ◽

Regulatory Motifs ◽

Functional Studies ◽

Maternal Mrna ◽

Mrna Population

Mechanisms providing for temporally complex patterns of maternal mRNA translation after fertilization are poorly understood. We employed bioinformatics analysis to compare populations of mRNAs enriched specifically on polysomes at the metaphase II (MII) stage oocyte and late one-cell stages and a detailed deletion/truncation series to identify elements that regulate translation. We used the Bag4 3′ untranslated region (UTR) as a model. Bioinformatics analysis revealed one conserved motif, subsequently confirmed by functional studies to be a key translation repressor element. The deletion/truncation studies revealed additional regulatory motifs, most notably a strong translation activator element of <30 nt. Analysis of mRNA secondary structure suggests that secondary structure plays a key role in translation repression. Additional bioinformatics analysis of the regulated mRNA population revealed a diverse collection of regulatory motifs found in small numbers of mRNAs, highlighting a high degree of sequence diversity and combinatorial complexity in the overall control of the maternal mRNA population. We conclude that translational control after fertilization is driven primarily by negative regulatory mechanisms opposing strong translational activators, with stage-specific release of the inhibitory influences to permit recruitment. The combination of bioinformatics analysis and deletion/truncation studies provides the necessary approach for dissecting postfertilization translation regulatory mechanisms.

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Transcriptional Activation of Arabidopsis Zygotes Is Required for Their Initial Division

10.1101/679035 ◽

2019 ◽

Author(s):

Ping Kao ◽

Michael Nodine

Keyword(s):

Transcriptional Activation ◽

Culture System ◽

Gene Products ◽

Zygotic Genome Activation ◽

Microscopy Technique ◽

Maternal To Zygotic Transition ◽

Parental Gene ◽

Active Transcription ◽

Genome Activation ◽

Zygotic Genome

SUMMARYCommonly referred to as the maternal-to-zygotic transition, the shift of developmental control from maternal-to-zygotic genomes is a key event during animal and plant embryogenesis. Together with the degradation of parental gene products, the increased transcriptional activities of the zygotic genome remodels the early embryonic transcriptome during this transition. Although evidence from multiple flowering plants suggests that zygotes become transcriptionally active soon after fertilization, the timing and developmental requirements of zygotic genome activation in Arabidopsis thaliana (Arabidopsis) remained a matter of debate until recently. In this report, we optimized an expansion microscopy technique for robust immunostaining of Arabidopsis ovules and seeds. This enabled the detection of marks indicative of active transcription in zygotes before the first cell division. Moreover, we employed a live-imaging culture system together with transcriptional inhibitors to demonstrate that such active transcription is required in zygotes. Our results indicate that zygotic genome activation occurs soon after fertilization and is physiologically required prior to the initial zygotic division in Arabidopsis.

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The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation

10.1101/598805 ◽

2019 ◽

Author(s):

Cai-Rong Yang ◽

Gabriel Rajkovic ◽

Enrico Maria Daldello ◽

Xuan G. Luong ◽

Jing Chen ◽

...

Keyword(s):

Oocyte Maturation ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Mrna Translation ◽

Critical Function ◽

Translational Repressor ◽

Maternal Mrna ◽

Maternal Transcripts ◽

Deleted In Azoospermia

AbstractDeleted in azoospermia like (DAZL) is an RNA-binding protein playing critical function during gamete development. In fully-grown oocytes, DAZL protein is detected in prophase and levels increase four to five fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this DAZL accumulation in maturing oocytes. Oocyte depletion of DAZL prevents progression to MII. This maturation block is associated with widespread disruption in the pattern of maternal transcripts loading on ribosomes and their translation measured using a RiboTag IP/RNASeq or qPCR strategy. In addition to decreased ribosome loading of a subset of transcripts, we found that DAZL depletion causes also translational activation of distinct subset of mRNAs. DAZL binds to mRNAs whose translation is both repressed and activated during oocyte maturation. Unexpectedly, DAZL depletion also causes increased ribosome loading of a subset of mRNAs in quiescent GV-arrested oocytes. This dual role of repression and activation is recapitulated by using YFP reporters including the 3’UTR of DAZL targets. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation of these targets as well as maturation to MII. Mutagenesis of putative DAZL-binding sites in these candidate mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs in mature oocytes, functioning both as translational repressor and activator.

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Regulatory principles governing the maternal-to-zygotic transition: insights from Drosophila melanogaster

Open Biology ◽

10.1098/rsob.180183 ◽

2018 ◽

Vol 8 (12) ◽

pp. 180183 ◽

Cited By ~ 16

Author(s):

Danielle C. Hamm ◽

Melissa M. Harrison

Keyword(s):

Drosophila Melanogaster ◽

Transcriptional Activation ◽

Fruit Fly ◽

Cell Types ◽

Parallel Mechanisms ◽

Molecular Events ◽

Connected Set ◽

Maternal To Zygotic Transition ◽

Adult Organism ◽

Zygotic Genome

The onset of metazoan development requires that two terminally differentiated germ cells, a sperm and an oocyte, become reprogrammed to the totipotent embryo, which can subsequently give rise to all the cell types of the adult organism. In nearly all animals, maternal gene products regulate the initial events of embryogenesis while the zygotic genome remains transcriptionally silent. Developmental control is then passed from mother to zygote through a process known as the maternal-to-zygotic transition (MZT). The MZT comprises an intimately connected set of molecular events that mediate degradation of maternally deposited mRNAs and transcriptional activation of the zygotic genome. This essential developmental transition is conserved among metazoans but is perhaps best understood in the fruit fly, Drosophila melanogaster . In this article, we will review our understanding of the events that drive the MZT in Drosophila embryos and highlight parallel mechanisms driving this transition in other animals.

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Xyloglucan processing machinery in Xanthomonas pathogens and its role in the transcriptional activation of virulence factors

Nature Communications ◽

10.1038/s41467-021-24277-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Plinio S. Vieira ◽

Isabela M. Bonfim ◽

Evandro A. Araujo ◽

Ricardo R. Melo ◽

Augusto R. Lima ◽

...

Keyword(s):

Virulence Factors ◽

Transcriptional Activation ◽

Molecular Mechanisms ◽

Model Organism ◽

Citrus Canker ◽

Effector Proteins ◽

Glycoside Hydrolases ◽

Host Cells ◽

System A ◽

Enzymatic Machinery

AbstractXyloglucans are highly substituted and recalcitrant polysaccharides found in the primary cell walls of vascular plants, acting as a barrier against pathogens. Here, we reveal that the diverse and economically relevant Xanthomonas bacteria are endowed with a xyloglucan depolymerization machinery that is linked to pathogenesis. Using the citrus canker pathogen as a model organism, we show that this system encompasses distinctive glycoside hydrolases, a modular xyloglucan acetylesterase and specific membrane transporters, demonstrating that plant-associated bacteria employ distinct molecular strategies from commensal gut bacteria to cope with xyloglucans. Notably, the sugars released by this system elicit the expression of several key virulence factors, including the type III secretion system, a membrane-embedded apparatus to deliver effector proteins into the host cells. Together, these findings shed light on the molecular mechanisms underpinning the intricate enzymatic machinery of Xanthomonas to depolymerize xyloglucans and uncover a role for this system in signaling pathways driving pathogenesis.

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In Search of Species-Specific SNPs in a Non-Model Animal (European Bison (Bison bonasus))—Comparison of De Novo and Reference-Based Integrated Pipeline of STACKS Using Genotyping-by-Sequencing (GBS) Data

Animals ◽

10.3390/ani11082226 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2226

Author(s):

Sazia Kunvar ◽

Sylwia Czarnomska ◽

Cino Pertoldi ◽

Małgorzata Tokarska

Keyword(s):

Reference Genome ◽

De Novo ◽

Bos Taurus ◽

Model Organism ◽

Genotyping By Sequencing ◽

Model Organisms ◽

European Bison ◽

Model Animal ◽

Pcr Duplicates ◽

Species Specific

The European bison is a non-model organism; thus, most of its genetic and genomic analyses have been performed using cattle-specific resources, such as BovineSNP50 BeadChip or Illumina Bovine 800 K HD Bead Chip. The problem with non-specific tools is the potential loss of evolutionary diversified information (ascertainment bias) and species-specific markers. Here, we have used a genotyping-by-sequencing (GBS) approach for genotyping 256 samples from the European bison population in Bialowieza Forest (Poland) and performed an analysis using two integrated pipelines of the STACKS software: one is de novo (without reference genome) and the other is a reference pipeline (with reference genome). Moreover, we used a reference pipeline with two different genomes, i.e., Bos taurus and European bison. Genotyping by sequencing (GBS) is a useful tool for SNP genotyping in non-model organisms due to its cost effectiveness. Our results support GBS with a reference pipeline without PCR duplicates as a powerful approach for studying the population structure and genotyping data of non-model organisms. We found more polymorphic markers in the reference pipeline in comparison to the de novo pipeline. The decreased number of SNPs from the de novo pipeline could be due to the extremely low level of heterozygosity in European bison. It has been confirmed that all the de novo/Bos taurus and Bos taurus reference pipeline obtained SNPs were unique and not included in 800 K BovineHD BeadChip.

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Quantitative investigation reveals distinct phases in Drosophila sleep

Communications Biology ◽

10.1038/s42003-021-01883-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Xiaochan Xu ◽

Wei Yang ◽

Binghui Tian ◽

Xiuwen Sui ◽

Weilai Chi ◽

...

Keyword(s):

Drosophila Melanogaster ◽

General Pattern ◽

Model Organism ◽

Infrared Camera ◽

Fruit Fly ◽

Genetic Dissection ◽

Power Law Distribution ◽

Quantitative Investigation ◽

Waking Up ◽

Set Up

AbstractThe fruit fly, Drosophila melanogaster, has been used as a model organism for the molecular and genetic dissection of sleeping behaviors. However, most previous studies were based on qualitative or semi-quantitative characterizations. Here we quantified sleep in flies. We set up an assay to continuously track the activity of flies using infrared camera, which monitored the movement of tens of flies simultaneously with high spatial and temporal resolution. We obtained accurate statistics regarding the rest and sleep patterns of single flies. Analysis of our data has revealed a general pattern of rest and sleep: the rest statistics obeyed a power law distribution and the sleep statistics obeyed an exponential distribution. Thus, a resting fly would start to move again with a probability that decreased with the time it has rested, whereas a sleeping fly would wake up with a probability independent of how long it had slept. Resting transits to sleeping at time scales of minutes. Our method allows quantitative investigations of resting and sleeping behaviors and our results provide insights for mechanisms of falling into and waking up from sleep.

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