Absence Of Transcription Research Articles

Brain-resident memory cells (bT RM) and virus reactivation

Abstract Background Neuroimmune responses terminate MCMV acute infection, however, a subset of neurons still harbor latent viral genomes. Factors regulating viral reactivation remain to be elucidated. Methods Using RNAscope, IE1 nucleic acid was detected within brains at D5 and D30 p.i. Using real-time RT-PCR, we assessed expression of IE1, E1, and gB transcripts. Using multi-color flow cytometry, we assessed depletion of bT RMfollowing icv injection of either α-CD8 Ab or α-CD103-sap. Using luciferase-expressing transgenic mice, we longitudinally assessed reactivation of cre-MCMV after T-cell depletion using live small animal imaging. Explant assay was employed to study the role of bT RMin reactivation. Using Nanostring, we identified changes following bT RM-depletion. Results Brain infection was demonstrated by X-gal staining as well as IE1 staining using RNAscope at 5 d p.i. After 30 d p.i., the virus established latency, as indicated by absence of transcripts (IE1, E1, and gB). After establishment, we injected either α-CD8 Ab or α-CD103-sap into the brain and showed 90–95% T-cell depletion. We infected mice with cre-MCMV, which expresses Cre recombinase. We observed enhanced imaging signals indicative of IE promoter activity in depleted animals. Surprisingly, we efficiently recovered virus from untreated mice, but not from those depleted of bT RM. Furthermore, on Nanostring analysis, we identified gpnmband hmox1, upregulated 11.48- and 6.7-fold following bT RMdepletion. Conclusion When we depleted bT RM, there was transient IE expression, sufficient to activate surveying microglia. This eventually resulted in a tissue-wide anti-viral state. These data provide new insights into the role of bT RMin controlling reactivation. This project was supported by award numbers NS-038836 from the National Institute of Neurological Disorders and Stroke

Abstract LB361: Li-Fraumeni syndrome-associated dimer-forming mutant p53 promotes transactivation-independent mitochondrial cell death

Abstract Mutations that occur within the oligomerization domain (OD) of the tumor suppressor p53 generally abolish p53 tetramerization and are associated with increased cancer susceptibility in Li-Fraumeni syndrome (LFS). Despite their prevalence, the impact of OD-mutant p53 proteins in cancer, especially beyond a loss of canonical p53 activity, has not been well elucidated. We sought to delineate the gain-of-function (GOF) vs. loss-of-function (LOF) activities of OD-mutant p53, specifically focusing on the LFS tumor-derived p53(A347D) variant. We obtained LFS patient-derived dermal fibroblasts heterozygous for the mutation and generated an allelic series of U2OS cancer cell lines expressing wild-type p53, heterozygous (p53+/AD) or homozygous (p53AD/AD) mutant p53 or no p53 (p53 KO). In contrast to wild-type p53, mutant p53(A347D) exclusively forms dimers in both fibroblasts and cancer cells and has lost the ability to bind and transactivate the majority of canonical p53 target genes, which yields comparable tumorigenic properties between mutant p53 and p53 KO cells. Mutant p53(A347D), however, displays neomorphic activities. Glycolysis and oxidative phosphorylation pathways are enriched in cells bearing p53(A347D) relative to both wild-type p53 and p53 KO cells. Furthermore, dimeric mutant p53 induces striking mitochondrial network aberration and preferentially associates with mitochondria to drive apoptotic cell death upon topoisomerase II inhibition in the absence of transcription. Ultimately, we describe dimeric mutant p53 as wielding a double-edged sword: driving tumorigenesis through LOF while gaining enhanced apoptogenic activity, thereby providing a potential basis for select therapeutic approaches. Citation Format: Joshua H. Choe, Tatsuya Kawase, An Xu, Asja Guzman, David R. Tong, Aleksandar Z. Obradovic, Ana M. Low-Calle, Bita Alaghebandan, Ananya Raghavan, Kaitlin Long, Paul M. Hwang, Joshua D. Schiffman, Yan Zhu, Ruiying Zhao, Dung-Fang Lee, Chen Katz, Carol L. Prives. Li-Fraumeni syndrome-associated dimer-forming mutant p53 promotes transactivation-independent mitochondrial cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB361.

The translation regulator Zar1l controls timing of meiosis in Xenopus oocytes.

Oocyte maturation and early embryo development occur in vertebrates in the near absence of transcription. Thus, sexual reproduction of vertebrates critically depends on the timely translation of mRNAs already stockpiled in the oocyte. Yet how translational activation of specific mRNAs is temporally coordinated is still incompletely understood. Here, we elucidate the function of Zar1l, a yet uncharacterized member of the Zar RNA-binding protein family, in Xenopus oocytes. Employing TRIM-Away, we demonstrate that loss of Zar1l accelerates hormone-induced meiotic resumption of Xenopus oocytes due to premature accumulation of the M-phase-promoting kinase cMos. We show that Zar1l is a constituent of a large ribonucleoparticle containing the translation repressor 4E-T and the central polyadenylation regulator CPEB1, and that it binds directly to the cMos mRNA. Partial, hormone-induced degradation of Zar1l liberates 4E-T from CPEB1, which weakens translational repression of mRNAs encoding cMos and likely additional M-phase-promoting factors. Thus, our study provides fundamental insights into the mechanisms that ensure temporally regulated translation of key cell cycle regulators during oocyte maturation, which is essential for sexual reproductivity.

Incorporation of CENP-A/CID into centromeres during early Drosophila embryogenesis does not require RNA polymerase II–mediated transcription

In many species, centromere identity is specified epigenetically by special nucleosomes containing a centromere-specific histone H3 variant, designated as CENP-A in humans and CID in Drosophila melanogaster. After partitioning of centromere-specific nucleosomes onto newly replicated sister centromeres, loading of additional CENP-A/CID into centromeric chromatin is required for centromere maintenance in proliferating cells. Analyses with cultured cells have indicated that transcription of centromeric DNA by RNA polymerase II is required for deposition of new CID into centromere chromatin. However, a dependence of centromeric CID loading on transcription is difficult to reconcile with the notion that the initial embryonic stages appear to proceed in the absence of transcription in Drosophila, as also in many other animal species. To address the role of RNA polymerase II–mediated transcription for CID loading in early Drosophila embryos, we have quantified the effects of alpha-amanitin and triptolide on centromeric CID-EGFP levels. Our analyses demonstrate that microinjection of these two potent inhibitors of RNA polymerase II–mediated transcription has at most a marginal effect on centromeric CID deposition during progression through the early embryonic cleavage cycles. Thus, we conclude that at least during early Drosophila embryogenesis, incorporation of CID into centromeres does not depend on RNA polymerase II–mediated transcription.

Peroxiredoxins couple metabolism and cell division in an ultradian cycle.

Redox cycles have been reported in ultradian, circadian and cell cycle-synchronized systems. Redox cycles persist in the absence of transcription and cyclin-CDK activity, indicating that cells harbor multiple coupled oscillators. Nonetheless, the causal relationships and molecular mechanisms by which redox cycles are embedded within ultradian, circadian or cell division cycles remain largely elusive. Yeast harbor an ultradian oscillator, the yeast metabolic cycle (YMC), which comprises metabolic/redox cycles, transcriptional cycles and synchronized cell division. Here, we reveal the existence of robust cycling of H2O2 and peroxiredoxin oxidation during the YMC and show that peroxiredoxin inactivation disrupts metabolic cycling and abolishes coupling with cell division. We find that thiol-disulfide oxidants and reductants predictably modulate the switching between different YMC metabolic states, which in turn predictably perturbs cell cycle entry and exit. We propose that oscillatory H2O2-dependent protein thiol oxidation is a key regulator of metabolic cycling and its coordination with cell division.

Transcription shapes genome-wide histone acetylation patterns

Histone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. Using immunoblot and chromatin immunoprecipitation-sequencing in S. cerevisiae, here we show that the majority of histone acetylation is dependent on transcription. This dependency is partially explained by the requirement of RNA polymerase II (RNAPII) for the interaction of H4 histone acetyltransferases (HATs) with gene bodies. Our data also confirms the targeting of HATs by transcription activators, but interestingly, promoter-bound HATs are unable to acetylate histones in the absence of transcription. Indeed, HAT occupancy alone poorly predicts histone acetylation genome-wide, suggesting that HAT activity is regulated post-recruitment. Consistent with this, we show that histone acetylation increases at nucleosomes predicted to stall RNAPII, supporting the hypothesis that this modification is dependent on nucleosome disruption during transcription. Collectively, these data show that histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.

The impact of transcription inhibition during in vitro maturation on the proteome of bovine oocytes†.

Proper oocyte maturation is a prerequisite for successful reproduction and requires the resumption of meiosis to the metaphase II stage (MII). In bovine oocytes, nuclear maturation has been shown to occur in in vitro maturing cumulus-enclosed oocytes (COCs) in the absence of transcription, but their developmental capacity is reduced compared to transcriptionally competent COCs. To assess the impact of transcription during in vitro maturation of bovine COCs on the quantitative oocyte proteome, a holistic nano-LC-MS/MS analysis of germinal vesicle oocytes and MII oocytes matured with or without addition of the transcription inhibitor actinomycin D (ActD) was carried out. Analyzing eight biological replicates for each of the three groups, a total of 2018 proteins was identified. These could be clearly classified into proteins depending or not depending on transcription during oocyte maturation. Proteins whose abundance increased after maturation irrespective of transcription inhibition - and hence independent of transcription - were related to the cell cycle, reflecting the progression of meiosis, and to cellular component organization, which is crucial for cytoplasmic maturation. In contrast, transcription-dependent proteins were associated with cell-cell adhesion and translation. Since a high rate of protein synthesis in oocytes has been shown to correlate with their developmental competence, oocyte maturation in transcriptionally impaired COCs is apparently disturbed. Our experiments reveal that impaired transcription during in vitro maturation of COCs has a substantial effect on specific components of the oocyte proteome, and that transcription is required for specific classes of oocyte proteins predominantly involved in translation.

Translational Control of Xenopus Oocyte Meiosis: Toward the Genomic Era.

The study of oocytes has made enormous contributions to the understanding of the G2/M transition. The complementarity of investigations carried out on various model organisms has led to the identification of the M-phase promoting factor (MPF) and to unravel the basis of cell cycle regulation. Thanks to the power of biochemical approaches offered by frog oocytes, this model has allowed to identify the core signaling components involved in the regulation of M-phase. A central emerging layer of regulation of cell division regards protein translation. Oocytes are a unique model to tackle this question as they accumulate large quantities of dormant mRNAs to be used during meiosis resumption and progression, as well as the cell divisions during early embryogenesis. Since these events occur in the absence of transcription, they require cascades of successive unmasking, translation, and discarding of these mRNAs, implying a fine regulation of the timing of specific translation. In the last years, the Xenopus genome has been sequenced and annotated, enabling the development of omics techniques in this model and starting its transition into the genomic era. This review has critically described how the different phases of meiosis are orchestrated by changes in gene expression. The physiological states of the oocyte have been described together with the molecular mechanisms that control the critical transitions during meiosis progression, highlighting the connection between translation control and meiosis dynamics.

The Role of Growth Hormone Receptor Isoforms and Their Effects in Bone Metabolism and Skeletal Fragility.

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

Activation‐induced cytidine deaminase can target multiple topologies of double‐stranded DNA in a transcription‐independent manner

Activation-induced cytidine deaminase (AID) mutates immunoglobulin genes and acts genome-wide. AID targets robustly transcribed genes, and purified AID acts on single-stranded (ss) but not double-stranded (ds) DNA oligonucleotides. Thus, it is believed that transcription is the generator of ssDNA for AID. Previous cell-free studies examining the relationship between transcription and AID targeting have employed a bacterial colony count assay wherein AID reverts an antibiotic resistance stop codon in plasmid substrates, leading to colony formation. Here, we established a novel assay where kb-long dsDNA of varying topologies is incubated with AID, with or without transcription, followed by direct sequencing. This assay allows for an unselected and in-depth comparison of mutation frequency and pattern of AID targeting in the absence of transcription or across a range of transcription dynamics. We found that without transcription, AID targets breathing ssDNA in supercoiled and, to a lesser extent, in relaxed dsDNA. The most optimal transcription only modestly enhanced AID action on supercoiled dsDNA in a manner dependent on RNA polymerase speed. These data suggest that the correlation between transcription and AID targeting may reflect transcription leading to AID-accessible breathing ssDNA patches naturally occurring in de-chromatinized dsDNA, as much as being due to transcription directly generating ssDNA.

Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment

Delineating how chromosomes fold at length scales beyond one megabase remains obscure relative to smaller-scale folding into TADs, loops, and nucleosomes. We find that rather than simply unfolding chromatin, histone hyperacetylation results in interactions between distant genomic loci separated by tens to hundreds of megabases, even in the absence of transcription. These hyperacetylated "megadomains" are formed by the BRD4-NUT fusion oncoprotein, interact both within and between chromosomes, and form a specific nuclear subcompartment that has elevated gene activity with respect to other subcompartments. Pharmacological degradation of BRD4-NUT results in collapse of megadomains and attenuation of the interactions between them. In contrast, these interactions persist and contacts between newly acetylated regions are formed after inhibiting RNA polymerase II initiation. Our structure-function approach thus reveals that broad chromatin domains of identical biochemical composition, independent of transcription, form nuclear subcompartments, and also indicates the potential of altering chromosome structure for treating human disease.

Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.

Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by Eμ enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of Eμ enhancer affects both transcription and recombination, making it difficult to conclude if Eμ controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of Eμ enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that Eμ controls transcription and recombination through distinct mechanisms. Moreover, while the normally Eμ-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.

Spatio-temporal expression of ANK2 promotes cytokinesis in oocytes

In the absence of transcription, the regulation of gene expression in oocytes is controlled almost exclusively at the level of transcriptome and proteome stabilization, and translation. A subset of maternal transcripts is stored in a translationally dormant state in the oocyte, and temporally driven translation of specific mRNAs propel meiotic progression, oocyte-to-embryo transition and early embryo development. We identified Ank2.3 as the only transcript variant present in the mouse oocyte and discovered that it is translated after nuclear envelope breakdown. Here we show that Ank2.3 mRNA is localized in higher concentration in the oocyte nucleoplasm and, after nuclear envelope breakdown, in the newly forming spindle where its translation occurs. Furthermore, we reveal that Ank2.3 mRNA contains an oligo-pyrimidine motif at 5′UTR that predetermines its translation through a cap-dependent pathway. Lastly, we show that prevention of ANK2 translation leads to abnormalities in oocyte cytokinesis.

Preserving Genome Integrity During the Early Embryonic DNA Replication Cycles.

During the very early stages of embryonic development chromosome replication occurs under rather challenging conditions, including a very short cell cycle, absence of transcription, a relaxed DNA damage response and, in certain animal species, a highly contracted S-phase. This raises the puzzling question of how the genome can be faithfully replicated in such a peculiar metabolic context. Recent studies have provided new insights into this issue, and unveiled that embryos are prone to accumulate genetic and genomic alterations, most likely due to restricted cellular functions, in particular reduced DNA synthesis quality control. These findings may explain the low rate of successful development in mammals and the occurrence of diseases, such as abnormal developmental features and cancer. In this review, we will discuss recent findings in this field and put forward perspectives to further study this fascinating question.

Novel functions of the ubiquitin-independent proteasome system in regulating Xenopus germline development.

In most species, early germline development occurs in the absence of transcription with germline determinants subject to complex translational and post-translational regulations. Here, we report for the first time that early germline development is influenced by dynamic regulation of the proteasome system, previously thought to be ubiquitously expressed and to serve 'housekeeping' roles in controlling protein homeostasis. We show that proteasomes are present in a gradient with the highest levels in the animal hemisphere and extending into the vegetal hemisphere of Xenopus oocytes. This distribution changes dramatically during the oocyte-to-embryo transition, with proteasomes becoming enriched in and restricted to the animal hemisphere and therefore separated from vegetally localized germline determinants. We identify Dead-end1 (Dnd1), a master regulator of vertebrate germline development, as a novel substrate of the ubiquitin-independent proteasomes. In the oocyte, ubiquitin-independent proteasomal degradation acts together with translational repression to prevent premature accumulation of Dnd1 protein. In the embryo, artificially increasing ubiquitin-independent proteasomal degradation in the vegetal pole interferes with germline development. Our work thus reveals novel inhibitory functions and spatial regulation of the ubiquitin-independent proteasome during vertebrate germline development.

BABA-Primed Histone Modifications in Potato for Intergenerational Resistance to Phytophthora infestans.

In this paper we analyzed β-aminobutyric acid (BABA)-primed epigenetic adjustment of potato cv. “Sarpo Mira” to Phytophthora infestans. The first stress-free generation of the potato genotype obtained from BABA-primed parent plants via tubers and seeds showed pronounced resistance to the pathogen, which was tuned with the transcriptional memory of SA-responsive genes. During the early priming phase before the triggering stress, we found robust bistable deposition of histone marks (H3K4me2 and H3K27me3) on the NPR1 (Non-expressor of PR genes) and the SNI1 gene (Suppressor of NPR1, Inducible), in which transcription antagonized silencing. Switchable chromatin states of these adverse systemic acquired resistance (SAR) regulators probably reprogrammed responsiveness of the PR1 and PR2 genes and contributed to stress imprinting. The elevated levels of heritable H3K4me2 tag in the absence of transcription on SA-dependent genes in BABA-primed (F0) and its vegetative and generative progeny (F1) before pathogen challenge provided evidence for the epigenetic mark for intergenerational memory in potato. Moreover, our study revealed that histone acetylation was not critical for maintaining BABA-primed defense information until the plants were triggered with the virulent pathogen when rapid and boosted PRs gene expression probably required histone acetyltransferase (HAT) activity both in F0 and F1 progeny.

Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs

The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis-regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells.

Use of quantitative real-time PCR to determine viability of Streptococcus equi subspecies equi in respiratory secretions from horses with strangles.

In recent years, molecular approaches have been able to characterise the viability of equine upper respiratory tract pathogens using absolute molecular quantitation as well as detection of transcripts for virulence genes. The objective of this study was to investigate molecular surrogates for S.equi subspecies equi (S.equi) viability in biological samples from horses with strangles. Retrospective cross-sectional study. S.equi culture-positive and culture-negative upper airway secretions were assessed by qPCR at the genomic (gDNA) and complimentary DNA (cDNA) level for various target genes (SeM, SEQ2190, eqbE and szpSe). Absolute quantitation was performed using standard curves, and the results were expressed as number of S.equi target genes per μl of gDNA or cDNA. Additionally, the presence or absence of S.equi gene expression for the various target genes was assessed and compared with the culture results. While all 21 culture-positive samples tested S.equiqPCR positive, up to 43.7 and 18.9% of 64 culture-negative samples tested qPCR positive at the gDNA and cDNA level, respectively. Significant differences in absolute quantitation for S.equi at the gDNA level were found between culture-positive and culture-negative samples. When absolute quantitation of S.equi target genes at the gDNA level was assessed with the presence or absence of transcripts, there was a significantly higher S.equi target gene number in samples with expression of transcripts compared with samples with no expression of transcripts. The lack of standardisation of samples collected in the field and the delay from sample collection to samples processing may have negatively affected the cultivability of S.equi and mRNA quality. Molecular viability for S.equi can be investigated by determining absolute quantitation and/or by detecting mRNA for specific target genes. However, veterinarians have to be cautioned that any qPCR-positive result for S.equi needs to be taken seriously and trigger biosecurity protocols aimed at reducing spread.

Expression of Alternative Ago2 Isoform Associated with Loss of microRNA-Driven Translational Repression in Mouse Oocytes

Mouse oocyte maturation, fertilization, and reprogramming occur in the absence of transcription, and thus, changes in mRNA levels and translation rate are regulated through post-transcriptional mechanisms [1]. Surprisingly, microRNA function, which is a major form of post-transcriptional regulation, is absent during this critical period of mammalian development [2, 3]. Here, we investigated the mechanisms underlying the global suppression of microRNA activity. In both mouse and frogs, microRNA function was active in growing oocytes but then absent during oocyte maturation. RNA sequencing (RNA-seq) of mouse oocytes uncovered that the microRNA effector protein AGO2 is predominantly expressed as an alternative isoform that encodes a truncated protein lacking all of the known essential domains. Full-length Ago2 as well as the related Argonautes (Ago1, Ago3, and Ago4) were lowly expressed in maturing mouse oocytes. Reintroduction of full-length AGO2 together with an exogenous microRNA in either mouse or frog oocytes restored translational repression of a target reporter. However, levels of endogenous transcripts remained unchanged. Consistent with a lack of microRNA activity, analysis of transcripts with alternative polyadenylation sites showed increased stability of transcripts with a longer 3' UTR during oocyte maturation. Redundant mechanisms protecting endogenous transcripts and the conserved loss of microRNA activity suggest a strong selection for suppressing microRNA function in vertebrate oocytes.

Maternal Ybx1 safeguards zebrafish oocyte maturation and maternal-to-zygotic transition by repressing global translation

Maternal mRNAs and proteins dictate early embryonic development before zygotic genome activation. In the absence of transcription, elaborate control of maternal mRNA translation is of particular importance for oocyte maturation and early embryogenesis. By analyzing zebrafish ybx1 mutants with a null allele, we demonstrate an essential role of maternal ybx1 in repressing global translation in oocytes and embryos. Loss of maternal Ybx1 leads to impaired oocyte maturation and egg activation. Maternal ybx1 (Mybx1) mutant embryos fail to undergo normal cleavage and the maternal-to-zygotic transition (MZT). Morpholino knockdown of ybx1 also results in MZT loss and epiboly failure, suggesting the postfertilization requirement of Ybx1. In addition, elevated global translation level and the unfolded protein response were found in Ybx1-depleted embryos. Supplementing translational repression by eIF4E inhibition markedly rescues the Mybx1 phenotype. Mechanistically, Ybx1 in embryos may associate with processing body components and repress translation when tethered to target mRNAs. Collectively, our results identify maternal Ybx1 as a global translational repressor required for oocyte maturation and early embryogenesis.