The molecular mechanisms underpinning maternal mRNA dormancy.

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

Heterogeneity in maternal mRNAs within clutches of eggs in response to thermal stress during the embryonic stage.

BACKGROUND: The origin of variation is of central interest in evolutionary biology. Maternal mRNAs govern early embryogenesis in many animal species, and we investigated the possibility that heterogeneity in maternal mRNA provisioning of eggs can be modulated by environmental stimuli. RESULTS: We employed two sibling species of the ascidian Ciona, called here types A and B, that are adapted to different temperature regimes and can be hybridized. Previous study showed that hybrids using type B eggs had higher susceptibility to thermal stress than hybrids using type A eggs. We conducted transcriptome analyses of multiple single eggs from crosses using eggs of the different species to compare the effects of maternal thermal stress on heterogeneity in egg provisioning, and followed the effects across generations. We found overall decreases of heterogeneity of egg maternal mRNAs associated with maternal thermal stress. When the eggs produced by the F1 AB generation were crossed with type B sperm and the progeny ('ABB' generation) reared unstressed until maturation, the overall heterogeneity of the eggs produced was greater in a clutch from an individual with a heat-stressed mother compared to one from a non-heat-stressed mother. By examining individual genes, we found no consistent overall effect of thermal stress on heterogeneity of expression in genes involved in developmental buffering. In contrast, heterogeneity of expression in signaling molecules was directly affected by thermal stress. CONCLUSIONS: Due to the absence of batch replicates and variation in the number of reads obtained, our conclusions are very limited. However, contrary to the predictions of bet-hedging, the results suggest that maternal thermal stress at the embryo stage is associated with reduced heterogeneity of maternal mRNA provision in the eggs subsequently produced by the stressed individual, but there is then a large increase in heterogeneity in eggs of the next generation, although itself unstressed. Despite its limitations, our study presents a proof of concept, identifying a model system, experimental approach and analytical techniques capable of providing a significant advance in understanding the impact of maternal environment on developmental heterogeneity.

Degradation and translation of maternal mRNA for embryogenesis.

Maternal mRNAs accumulate during egg growth and must be judiciously degraded or translated to ensure successful development of mammalian embryos. In this review we integrate recent investigations into pathways controlling rapid degradation of maternal mRNAs during the maternal-to-zygotic transition. Degradation is not indiscriminate, and some mRNAs are selectively protected and rapidly translated after fertilization for reprogramming the zygotic genome during early embryogenesis. Oocyte specific cofactors and pathways have been illustrated to control different futures of maternal mRNAs. We discuss mechanisms that control the fate of maternal mRNAs during late oogenesis and after fertilization. Issues to be resolved in current maternal mRNA research are described, and future research directions are proposed.

eIF4E1b is a non-canonical eIF4E protecting maternal dormant mRNAs.

Maternal mRNAs are essential for protein synthesis during oogenesis and early embryogenesis. To adapt translation to specific needs during development, maternal mRNAs are translationally repressed by shortening the polyA tails. While mRNA deadenylation is associated with decapping and degradation in somatic cells, maternal mRNAs with short polyA tails are stable. Here we report that the germline-specific eIF4E paralog, eIF4E1b, is essential for zebrafish oogenesis. eIF4E1b localizes to P-bodies in zebrafish embryos and binds to mRNAs with reported short or no polyA tails, including histone mRNAs. Loss of eIF4E1b results in reduced histone mRNA levels in early gonads, consistent with a role in mRNA storage. Using mouse and human eIF4E1Bs (in vitro) and zebrafish eIF4E1b (in vivo), we show that unlike canonical eIF4Es, eIF4E1b does not interact with eIF4G to initiate translation. Instead, eIF4E1b interacts with the translational repressor eIF4ENIF1, which is required for eIF4E1b localization to P-bodies. Our study is consistent with an important role of eIF4E1b in regulating mRNA dormancy and provides new insights into fundamental post-transcriptional regulatory principles governing early vertebrate development.

Predictive modeling of oocyte maternal mRNA features for five mammalian species reveals potential shared and species-restricted regulators during maturation.

Oocyte maturation is accompanied by changes in abundances of thousands of mRNAs, many degraded and many preferentially stabilized. mRNA stability can be regulated by diverse features including GC content, codon bias, and motifs within the 3'-untranslated region (UTR) interacting with RNA binding proteins (RBPs) and miRNAs. Many studies have identified factors participating in mRNA splicing, bulk mRNA storage, and translational recruitment in mammalian oocytes, but the roles of potentially hundreds of expressed factors, how they regulate cohorts of thousands of mRNAs, and to what extent their functions are conserved across species has not been determined. We performed an extensive in silico cross-species analysis of features associated with mRNAs of different stability classes during oocyte maturation (stable, moderately degraded, and highly degraded) for five mammalian species. Using publicly available RNA sequencing data for germinal vesicle (GV) and MII oocyte transcriptomes, we determined that 3'-UTR length and synonymous codon usage are positively associated with stability, while greater GC content is negatively associated with stability. By applying machine learning and feature selection strategies, we identified RBPs and miRNAs that are predictive of mRNA stability, including some across multiple species and others more species-restricted. The results provide new insight into the mechanisms regulating maternal mRNA stabilization or degradation.NEW & NOTEWORTHY Conservation across species of mRNA features regulating maternal mRNA stability during mammalian oocyte maturation was analyzed. 3'-Untranslated region length and synonymous codon usage are positively associated with stability, while GC content is negatively associated. Just three RNA binding protein motifs were predicted to regulate mRNA stability across all five species examined, but associated pathways and functions are shared, indicating oocytes of different species arrive at comparable physiological destinations via different routes.

LSM14B is essential for oocyte meiotic maturation by regulating maternal mRNA storage and clearance.

Fully grown oocytes remain transcriptionally quiescent, yet many maternal mRNAs are synthesized and retained in growing oocytes. We now know that maternal mRNAs are stored in a structure called the mitochondria-associated ribonucleoprotein domain (MARDO). However, the components and functions of MARDO remain elusive. Here, we found that LSM14B knockout prevents the proper storage and timely clearance of mRNAs (including Cyclin B1, Btg4 and other mRNAs that are translationally activated during meiotic maturation), specifically by disrupting MARDO assembly during oocyte growth and meiotic maturation. With decreased levels of storage and clearance, the LSM14B knockout oocytes failed to enter meiosis II, ultimately resulting in female infertility. Our results demonstrate the function of LSM14B in MARDO assembly, and couple the MARDO with mRNA clearance and oocyte meiotic maturation.

Parallels and contrasts between the cnidarian and bilaterian maternal-to-zygotic transition are revealed in Hydractinia embryos.

Embryogenesis requires coordinated gene regulatory activities early on that establish the trajectory of subsequent development, during a period called the maternal-to-zygotic transition (MZT). The MZT comprises transcriptional activation of the embryonic genome and post-transcriptional regulation of egg-inherited maternal mRNA. Investigation into the MZT in animals has focused almost exclusively on bilaterians, which include all classical models such as flies, worms, sea urchin, and vertebrates, thus limiting our capacity to understand the gene regulatory paradigms uniting the MZT across all animals. Here, we elucidate the MZT of a non-bilaterian, the cnidarian Hydractinia symbiolongicarpus. Using parallel poly(A)-selected and non poly(A)-dependent RNA-seq approaches, we find that the Hydractinia MZT is composed of regulatory activities similar to many bilaterians, including cytoplasmic readenylation of maternally contributed mRNA, delayed genome activation, and separate phases of maternal mRNA deadenylation and degradation that likely depend on both maternally and zygotically encoded clearance factors, including microRNAs. But we also observe massive upregulation of histone genes and an expanded repertoire of predicted H4K20 methyltransferases, aspects thus far particular to the Hydractinia MZT and potentially underlying a novel mode of early embryonic chromatin regulation. Thus, similar regulatory strategies with taxon-specific elaboration underlie the MZT in both bilaterian and non-bilaterian embryos, providing insight into how an essential developmental transition may have arisen in ancestral animals.

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

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

Maternal patterns of inheritance alter transcript expression in eggs.

BACKGROUND: Modifications to early development can lead to evolutionary diversification. The early stages of development are under maternal control, as mothers produce eggs loaded with nutrients, proteins and mRNAs that direct early embryogenesis. Maternally provided mRNAs are the only expressed genes in initial stages of development and are tightly regulated. Differences in maternal mRNA provisioning could lead to phenotypic changes in embryogenesis and ultimately evolutionary changes in development. However, the extent that maternal mRNA expression in eggs can vary is unknown for most developmental models. Here, we use a species with dimorphic development- where females make eggs and larvae of different sizes and life-history modes-to investigate the extent of variation in maternal mRNA provisioning to the egg. RESULTS: We find that there is significant variation in gene expression across eggs of different development modes, and that there are both qualitative and quantitative differences in mRNA expression. We separate parental effects from allelic effects, and find that both mechanisms contribute to mRNA expression differences. We also find that offspring of intraspecific crosses differentially provision their eggs based on the parental cross direction (a parental effect), which has not been previously demonstrated in reproductive traits like oogenesis. CONCLUSION: We find that maternally controlled initiation of development is functionally distinct between eggs of different sizes and maternal genotypes. Both allele-specific effects and parent-of-origin effects contribute to gene expression differences in eggs. The latter indicates an intergenerational effect where a parent's genotype can affect gene expression in an egg made by the next generation.

Sperm-borne microRNA-34c regulates maternal mRNA degradation and preimplantation embryonic development in mice.

BACKGROUND: Studies have shown that sperm-borne microRNAs (miRNAs) are involved in mammalian preimplantation embryonic development. In humans, spermatozoan miR-34c levels are correlated with in vitro fertilization outcomes, such as embryo quality and the clinical pregnancy and live birth rates. In rabbits and cows, miR-34c improves the developmental competence of embryos generated by somatic cell nuclear transfer. However, the mechanisms underlying the regulation of embryonic development by miR-34c remain unknown. METHODS: Female C57BL/6 mice (6-8 weeks old) were superovulated, and pronucleated zygotes were collected and microinjected with an miR-34c inhibitor or a negative-control RNA. The embryonic development of the microinjected zygotes was evaluated, and the messenger RNA (mRNA) expression profiles of the embryos at the two-cell, four-cell and blastocyst stages (five embryos per group) were determined by RNA sequencing analysis. Gene expression levels were verified by reverse transcription-quantitative polymerase chain reaction. Cluster analysis and heat map visualization were performed to detect differentially expressed mRNAs. Pathway and process enrichment analyses were performed using ontology resources. Differentially expressed mRNAs were systematically analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins database to determine their biological functions. RESULTS: Embryonic developmental potential was significantly reduced in zygotes microinjected with the miR-34c inhibitor compared with those microinjected with a negative-control RNA. Two-cell stage embryos microinjected with an miR-34c inhibitor presented altered transcriptomic profiles, with upregulated expression of maternal miR-34c target mRNAs and classical maternal mRNAs. Differentially expressed transcripts were mainly of genes associated with lipid metabolism and cellular membrane function at the two-cell stage, with cell-cycle phase transition and energy metabolism at the four-cell stage; and with vesicle organization, lipid biosynthetic process and endomembrane system organization at the blastocyst stage. We also showed that genes related to preimplantation embryonic development, including Alkbh4, Sp1, Mapk14, Sin3a, Sdc1 and Laptm4b, were significantly downregulated after microinjection of an miR-34c inhibitor. CONCLUSIONS: Sperm-borne miR-34c may regulate preimplantation embryonic development by affecting multiple biological processes, such as maternal mRNA degradation, cellular metabolism, cell proliferation and blastocyst implantation. Our data demonstrate the importance of sperm-derived miRNAs in the development of preimplantation embryos.

LSM14B is an Oocyte-Specific RNA-Binding Protein Indispensable for Maternal mRNA Metabolism and Oocyte Development in Mice.

Mammalian oogenesis features reliance on the mRNAs produced and stored during early growth phase. These are essential for producing an oocyte competent to undergo meiotic maturation and embryogenesis later when oocytes are transcriptionally silent. The fate of maternal mRNAs hence ensures the success of oogenesis and the quality of the resulting eggs. Nevertheless, how the fate of maternal mRNAs is determined remains largely elusive. RNA-binding proteins (RBPs) are crucial regulators of oogenesis, yet the identity of the full complement of RBPs expressed in oocytes is unknown. Here, a global view of oocyte-expressed RBPs is presented: mRNA-interactome capture identifies 1396 RBPs in mouse oocytes. An analysis of one of these RBPs, LSM family member 14 (LSM14B), demonstrates that this RBP is specific to oocytes and associated with many networks essential for oogenesis. Deletion of Lsm14b results in female-specific infertility and a phenotype characterized by oocytes incompetent to complete meiosis and early embryogenesis. LSM14B serves as an interaction hub for proteins and mRNAs throughout oocyte development and regulates translation of a subset of its bound mRNAs. Therefore, RNP complexes tethered by LSM14B are found exclusively in oocytes and are essential for the control of maternal mRNA fate and oocyte development.

Spatiotemporal regulation of maternal mRNAs during vertebrate oocyte meiotic maturation.

Vertebrate oocytes face a particular challenge concerning the regulation of gene expression during meiotic maturation. Global transcription becomes quiescent in fully grown oocytes, remains halted throughout maturation and fertilization, and only resumes upon embryonic genome activation. Hence, the oocyte meiotic maturation process is largely regulated by protein synthesis from pre-existing maternal messenger RNAs (mRNAs) that are transcribed and stored during oocyte growth. Rapidly developing genome-wide techniques have greatly expanded our insights into the global translation changes and possible regulatory mechanisms during oocyte maturation. The storage, translation, and processing of maternal mRNAs are thought to be regulated by factors interacting with elements in the mRNA molecules. Additionally, posttranscriptional modifications of mRNAs, such as methylation and uridylation, have recently been demonstrated to play crucial roles in maternal mRNA destabilization. However, a comprehensive understanding of the machineries that regulate maternal mRNA fate during oocyte maturation is still lacking. In particular, how the transcripts of important cell cycle components are stabilized, recruited at the appropriate time for translation, and eliminated to modulate oocyte meiotic progression remains unclear. A better understanding of these mechanisms will provide invaluable insights for the preconditions of developmental competence acquisition, with important implications for the treatment of infertility. This review discusses how the storage, localization, translation, and processing of oocyte mRNAs are regulated, and how these contribute to oocyte maturation progression.

Maternal mRNA deadenylation and allocation via Rbm14 condensates facilitate vertebrate blastula development.

Early embryonic development depends on proper utilization and clearance of maternal transcriptomes. How these processes are spatiotemporally regulated remains unclear. Here we show that nuclear RNA-binding protein Rbm14 and maternal mRNAs co-phase separate into cytoplasmic condensates to facilitate vertebrate blastula-to-gastrula development. In zebrafish, Rbm14 condensates were highly abundant in blastomeres and markedly reduced after prominent activation of zygotic transcription. They concentrated at spindle poles by associating with centrosomal γ-tubulin puncta and displayed mainly asymmetric divisions with a global symmetry across embryonic midline in 8- and 16-cell embryos. Their formation was dose-dependently stimulated by m6 A, but repressed by m5 C modification of the maternal mRNA. Furthermore, deadenylase Parn co-phase separated with these condensates, and this was required for deadenylation of the mRNAs in early blastomeres. Depletion of Rbm14 impaired embryonic cell differentiations and full activations of the zygotic genome in both zebrafish and mouse and resulted in developmental arrest at the blastula stage. Our results suggest that cytoplasmic Rbm14 condensate formation regulates early embryogenesis by facilitating deadenylation, protection, and mitotic allocation of m6 A-modified maternal mRNAs, and by releasing the poly(A)-less transcripts upon regulated disassembly to allow their re-polyadenylation and translation or clearance.

RNA-methyltransferase Nsun5 controls the maternal-to-zygotic transition by regulating maternal mRNA stability.

BACKGROUND: RNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m5 C (5-methylcytosine)-coordinating modificatory transcripts are dynamically regulated during oogenesis, and ovarian development is unknown. The purpose of this study was to determine whether NOP2/Sun RNA methyltransferase 5 (Nsun5) deletion leads to suppression of ovarian function and arrest of embryonic development. The regulation of mRNA decay and stability by m5 C modification is essential at multiple stages during the maternal-to-zygotic (MZT) transition. METHODS: Mouse ovaries and oocytes with Nsun5KO and the KGN cell line were subjected to m5 C identification, alternative splicing analysis and protein expression. BS-m5 C-seq, real-time polymerase chain reaction, Western blot, immunofluorescence and actinomycin D treatment assays were used. In particular, BS-m5 C-seq revealed a dynamic pattern of m5 C sites and genes in the ovaries between Nsun5KO and WT mice at the 2-month and 6-month stages. Diverse bioinformatic tools were employed to identify target genes for Nsun5. RESULTS: Here, a maternal mRNA stability study showed that deletion of the m5 C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m5 C revealed that the level of m5 C decreased in a time-dependent manner after Nsun5 knockout. Regarding the molecular mechanism, we found that Nsun5 deficiency caused a m5 C decline in the exon and 3'UTR regions that influenced the translation efficiency of Mitotic arrest deficient 2 like 2 (MAD2L2) and Growth differentiation factor 9 (GDF9) in the ovary. Mechanistic investigation of alternative splicing indicated that Nsun5KO triggers aberrant events in the exon region of Brd8. CONCLUSIONS: Nsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m5 C-regulated maternal mRNA stabilization is essential for MZT transition.

Germline immortality relies on TRIM32-mediated turnover of a maternal mRNA activator in C. elegans.

How the germ line achieves a clean transition from maternal to zygotic gene expression control is a fundamental problem in sexually reproducing organisms. Whereas several mechanisms terminate the maternal program in the soma, this combined molecular reset and handover are poorly understood for primordial germ cells (PGCs). Here, we show that GRIF-1, a TRIM32-related and presumed E3 ubiquitin ligase in Caenorhabditis elegans, eliminates the maternal cytoplasmic poly(A) polymerase (cytoPAP) complex by targeting the germline-specific intrinsically disordered region of its enzymatic subunit, GLD-2, for proteasome-mediated degradation. Interference with cytoPAP turnover in PGCs causes frequent transgenerational sterility and, eventually, germline mortality. Hence, positively acting maternal RNA regulators are cleared via the proteasome system to avoid likely interference between maternal and zygotic gene expression programs to maintain transgenerational fertility and acquire germline immortality. This strategy is likely used in all animals that preform their immortal germ line via maternally inherited germplasm determinants.

Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment.

Full-grown oocytes are transcriptionally silent and must stably maintain the messenger RNAs (mRNAs) needed for oocyte meiotic maturation and early embryonic development. However, where and how mammalian oocytes store maternal mRNAs is unclear. Here, we report that mammalian oocytes accumulate mRNAs in a mitochondria-associated ribonucleoprotein domain (MARDO). MARDO assembly around mitochondria was promoted by the RNA-binding protein ZAR1 and directed by an increase in mitochondrial membrane potential during oocyte growth. MARDO foci coalesced into hydrogel-like matrices that clustered mitochondria. Maternal mRNAs stored in the MARDO were translationally repressed. Loss of ZAR1 disrupted the MARDO, dispersed mitochondria, and caused a premature loss of MARDO-localized mRNAs. Thus, a mitochondria-associated membraneless compartment controls mitochondrial distribution and regulates maternal mRNA storage, translation, and decay to ensure fertility in mammals.

LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs.

Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X-related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific Fxr1 ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation-deficient FXR1L351P mutation in Fxr1 knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.

Phase separation of Ddx3xb helicase regulates maternal-to-zygotic transition in zebrafish.

Vertebrate embryogenesis involves a conserved and fundamental process, called the maternal-to-zygotic transition (MZT), which marks the switch from a maternal factors-dominated state to a zygotic factors-driven state. Yet the precise mechanism underlying MZT remains largely unknown. Here we report that the RNA helicase Ddx3xb in zebrafish undergoes liquid-liquid phase separation (LLPS) via its N-terminal intrinsically disordered region (IDR), and an increase in ATP content promotes the condensation of Ddx3xb during MZT. Mutant form of Ddx3xb losing LLPS ability fails to rescue the developmental defect of Ddx3xb-deficient embryos. Interestingly, the IDR of either FUS or hnRNPA1 can functionally replace the N-terminal IDR in Ddx3xb. Phase separation of Ddx3xb facilitates the unwinding of 5' UTR structures of maternal mRNAs to enhance their translation. Our study reveals an unprecedent mechanism whereby the Ddx3xb phase separation regulates MZT by promoting maternal mRNA translation.

Developmental mRNA m5C landscape and regulatory innovations of massive m5C modification of maternal mRNAs in animals.

m5C is one of the longest-known RNA modifications, however, its developmental dynamics, functions, and evolution in mRNAs remain largely unknown. Here, we generate quantitative mRNA m5C maps at different stages of development in 6 vertebrate and invertebrate species and find convergent and unexpected massive methylation of maternal mRNAs mediated by NSUN2 and NSUN6. Using Drosophila as a model, we reveal that embryos lacking maternal mRNA m5C undergo cell cycle delays and fail to timely initiate maternal-to-zygotic transition, implying the functional importance of maternal mRNA m5C. From invertebrates to the lineage leading to humans, two waves of m5C regulatory innovations are observed: higher animals gain cis-directed NSUN2-mediated m5C sites at the 5' end of the mRNAs, accompanied by the emergence of more structured 5'UTR regions; humans gain thousands of trans-directed NSUN6-mediated m5C sites enriched in genes regulating the mitotic cell cycle. Collectively, our studies highlight the existence and regulatory innovations of a mechanism of early embryonic development and provide key resources for elucidating the role of mRNA m5C in biology and disease.

Profiling and functional characterization of maternal mRNA translation during mouse maternal-to-zygotic transition.

Translational regulation plays an important role in gene expression and function. Although the transcriptional dynamics of mouse preimplantation embryos have been well characterized, the global mRNA translation landscape and the master regulators of zygotic genome activation (ZGA) remain unknown. Here, by developing and applying a low-input ribosome profiling (LiRibo-seq) technique, we profiled the mRNA translation landscape in mouse preimplantation embryos and revealed the translational dynamics during mouse preimplantation development. We identified a marked translational transition from MII oocytes to zygotes and demonstrated that active translation of maternal mRNAs is essential for maternal-to-zygotic transition (MZT). We further showed that two maternal factors, Smarcd2 and Cyclin T2, whose translation is activated in zygotes, are required for chromatin reprogramming and ZGA, respectively. Our study thus not only filled in a knowledge gap on translational regulation during mammalian preimplantation development but also revealed insights into the critical function of maternal mRNA translation in MZT.