RNA m6A methylome in mouse oocytes and preimplantation embryos
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE192440 | GEO | 2023/02/10
REPOSITORIES: GEO
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Project description:Background: Maternal and zygotic mRNAs play critical roles in maternal-to-zygotic transition (MZT) stage and N6-methyladenosine (m6A) has been proven as an important RNA metabolism regulation system. However, the dynamic profiles of m6A modification during mammalian MZT and its potential functions remain largely unknown. Results: Here we utilized m6A-seq, low-input RNA-seq, LiRibo-seq and low-input proteomic analysis to examine the mRNA regulation dynamics during mouse MZT. We found that m6A could be inherited from maternal origin or de novo added after fertilization. Interestingly, we observed the de novo m6A modification on mRNA during zygotic genome activation (ZGA), especially at major ZGA. Further analysis showed that m6A modification on maternal mRNAs not only correlates with mRNA degradation after fertilization, but also maintains the stability of a small group of mRNAs thereby promoting their translation after fertilization. Using CRISPR-Cas13d mediated RNA editing, we systemically evaluated the functions of ten m6A regulators and identified Ythdc1 and Ythdf2 as key m6A readers for mouse preimplantation development. By combining low-input RNA-seq, RNA immunoprecipitation (RIP) and qRT-PCR, we uncovered and verified that Ythdc1 can associate with a small group of m6A-tagged mRNAs and participate in their mRNA stability regulation. Conclusions: Our integrated multi-omic analysis links m6A modification to the diverse fates of maternal and zygotic mRNAs and establishes a key role of m6A mediated RNA metabolism in mammalian MZT.
2023-03-28 | GSE228201 | GEO
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. It is initiated by maternal mRNAs and proteins during the period of zygotic genome quiescence after fertilization, followed by a gradual switch to zygotic genome activation and accompanied by clearance of maternal RNAs and proteins. A key question for embryonic development is how MZT process is regulated. Here we used a low-input proteomic analysis to measure the proteomic dynamics during early development of mouse maternal-to-zygotic transition.
2023-03-27 | PXD041023 | Pride
Project description:Background: Metazoan embryos undergo a maternal-to-zygotic transition (MZT) during which a subset of maternal gene products is eliminated and the zygotic genome becomes transcriptionally active. RNA-binding proteins (RBPs) and the microRNA-induced silencing complex (miRISC) â of which Argonaute 1 (AGO1) is a key component in Drosophila â target maternal mRNAs for degradation. The Drosophila Smaug, Brain tumor (BRAT) and Pumilio (PUM) RBPs direct the degradation of maternal mRNAs. Here we elucidate Smaugâs roles in regulation of miRNAs and miRISC during the MZT. Results: By global analysis of small RNAs at several stages during the MZT, we show that the vast majority of all miRNA species encoded by the Drosophila genome (85%) are expressed during the MZT. Whereas a subset of these miRNAs is loaded into oocytes by the mother and stays at constant levels during the MZT, dozens of miRNA species are either newly synthesized or re-expressed in the early embryo. Loss of Smaug has a profound effect on miRNAs but little effect on piRNAs or siRNAs. Smaug is required for production of new miRNAs during the MZT; Smaug-bound AGO1 reflects the constellation and abundance of the miRNAs present in early embryos; and Smaug is required for the increase in AGO1 protein levels that occurs during the MZT. As a consequence of low miRISC activity in smaug mutants, maternal mRNAs that are normally targeted for degradation by zygotic miRNAs fail to be cleared. BRAT and PUM share target mRNAs with miRISC during the MZT while the miR-309 miRNA family coregulates targets of BRAT but not PUM. Conclusions: Smaug controls the MZT through direct targeting of a subset of maternal mRNAs for degradation and, indirectly, through production and function of miRNAs and miRISC, which control clearance of a distinct subset of maternal mRNAs. BRAT and/or PUM function together with miRISC during the latter process. With respect to miRISC-dependent transcript degradation, Smaug is required (1) for the synthesis of miRNAs, (2) for synthesis and stabilization of AGO1, and (3) for action of AGO1 in association with its bound miRNAs. In smaug mutants a large number of maternal mRNAs persist and the MZT fails. Examination of miRNA expresssion at different time points in wild type and smuag mutant early embryos .
2016-09-06 | E-GEOD-82194 | biostudies-arrayexpress
Project description:In animal embryos the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents over half of the protein coding capacity of the Drosophila melanogaster genome and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). While the ubiquitin-proteasome system is necessary for clearance of all four repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL and ME31B for degradation early in the MZT; the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG makes the protein immune to degradation. We show that artificially persistent SMG downregulates the zygotic re-expression of mRNAs whose maternal contribution is cleared by SMG. Thus, clearance of SMG permits an orderly MZT.
2021-09-09 | PXD018794 | Pride
Project description:In animal embryos the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents over half of the protein coding capacity of the Drosophila melanogaster genome and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). While the ubiquitin-proteasome system is necessary for clearance of all four repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL and ME31B for degradation early in the MZT; the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG make it immune to degradation. We show that artificially persistent SMG downregulates the zygotic re-expression of mRNAs whose maternal contribution is cleared by SMG. Thus, clearance of SMG permits an orderly MZT.
2020-06-05 | PXD016523 | Pride
Project description:Upon fertilization, maternal factors direct development in a transcriptionally silent embryo. At the maternal-to-zygotic transition (MZT), a universal step in animal development, unknown maternal factors trigger zygotic genome activation (ZGA). In zebrafish, ZGA is required for gastrulation and clearance of maternal mRNAs, which is achieved in part by the conserved microRNA miR-430. However, the precise factors that activate the zygotic program remain largely unknown. Here we show that Nanog, Pou5f1 and SoxB1 are required for genome activation in zebrafish. We identified several hundred genes directly activated by maternal factors, thus constituting the first wave of zygotic transcription in zebrafish. Ribosome profiling in the pre-MZT embryo revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factor mRNAs. Combined loss of function for Nanog, SoxB1 and Pou5f1 resulted in developmental arrest prior to gastrulation, and a failure to activate >75% of zygotic genes. Furthermore, we found that Nanog binds the miR-430 locus and together with Pou5f1 and SoxB1 initiate miR-430 expression and activity. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and in turn trigger the clearance of the maternal program by activating miR-430 expression. Wild type and loss-of-function total mRNA sequencing of embryonic transcriptomes pre- and post-MZT; ribosome profiling pre-MZT
2013-09-22 | E-GEOD-47558 | biostudies-arrayexpress
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. Metaphase II (MII) oocytes and zygotes (one-cell embryo) serve as the mature oocyte and the initiation of pre-implantation embryo development respectively, and characterizing their molecular landscapes at protein levels plays an important role in uncovering MZT and zygotic genome activation (ZGA )in mammals. Here we used an ultrasensitive proteomic approach to depict an in-depth landscape for the very early stage of mouse MZT.
2023-05-23 | PXD041399 | Pride
Project description:In animal embryos the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents over half of the protein coding capacity of the Drosophila melanogaster genome and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). While the ubiquitin-proteasome system is necessary for clearance of all four repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL and ME31B for degradation early in the MZT; the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG makes the protein immune to degradation. We show that artificially persistent SMG downregulates the zygotic re-expression of mRNAs whose maternal contribution is cleared by SMG. Thus, clearance of SMG permits an orderly MZT
2020-05-18 | MSV000085442 | MassIVE
Project description:In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal to zygotic transition (MZT). During this time maternal RNAs are degraded and zygotic RNAs are transcribed1. A long standing question has been, what factors regulate these events? The recent findings that microRNAs and Smaugs mediate maternal transcript degradation brought new life to this old problem2,3, however, the transcription factors that activate zygotic gene expression remained elusive. A clue came from the finding that many early zygotic genes in Drosophila share a cis-regulatory heptamer motif, CAGGTAG and related sequences, collectively referred to as TAG-team sites4,5. We asked whether there was a dedicated transcription factor that interacts with these sites to activate early genes. Here we report the discovery of a zinc-finger protein, Zelda (Zld) that binds specifically to TAG-team sites, and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in the cellularization process, and fail to activate the transcription of many early zygotic genes involved in cellularization, sex determination, and dorsoventral patterning. Global expression profiling confirmed that Zld plays a key role in the activation of the early zygotic genome, and suggests that Zld may also play a role in maternal RNA degradation during the MZT since many RNAs are up-regulated in the absence of Zld. Keywords: Drosophila early embryo, MZT, transcriptional activator
2008-11-17 | GSE11231 | GEO
Project description:Background: Metazoan embryos undergo a maternal-to-zygotic transition (MZT) during which a subset of maternal gene products is eliminated and the zygotic genome becomes transcriptionally active. RNA-binding proteins (RBPs) and the microRNA-induced silencing complex (miRISC) – of which Argonaute 1 (AGO1) is a key component in Drosophila – target maternal mRNAs for degradation. The Drosophila Smaug, Brain tumor (BRAT) and Pumilio (PUM) RBPs direct the degradation of maternal mRNAs. Here we elucidate Smaug’s roles in regulation of miRNAs and miRISC during the MZT. Results: By global analysis of small RNAs at several stages during the MZT, we show that the vast majority of all miRNA species encoded by the Drosophila genome (85%) are expressed during the MZT. Whereas a subset of these miRNAs is loaded into oocytes by the mother and stays at constant levels during the MZT, dozens of miRNA species are either newly synthesized or re-expressed in the early embryo. Loss of Smaug has a profound effect on miRNAs but little effect on piRNAs or siRNAs. Smaug is required for production of new miRNAs during the MZT; Smaug-bound AGO1 reflects the constellation and abundance of the miRNAs present in early embryos; and Smaug is required for the increase in AGO1 protein levels that occurs during the MZT. As a consequence of low miRISC activity in smaug mutants, maternal mRNAs that are normally targeted for degradation by zygotic miRNAs fail to be cleared. BRAT and PUM share target mRNAs with miRISC during the MZT while the miR-309 miRNA family coregulates targets of BRAT but not PUM. Conclusions: Smaug controls the MZT through direct targeting of a subset of maternal mRNAs for degradation and, indirectly, through production and function of miRNAs and miRISC, which control clearance of a distinct subset of maternal mRNAs. BRAT and/or PUM function together with miRISC during the latter process. With respect to miRISC-dependent transcript degradation, Smaug is required (1) for the synthesis of miRNAs, (2) for synthesis and stabilization of AGO1, and (3) for action of AGO1 in association with its bound miRNAs. In smaug mutants a large number of maternal mRNAs persist and the MZT fails.
2016-09-06 | GSE82194 | GEO