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The role of ALKBH5 in maternal RNA decay during mammalian oocyte meiosis

ABSTRACT: To investigate the function of ALKBH5 in the regulation of maternal RNA decay during mice oocyte meiosis, we established Alkbh5 knockout mice and analyzed the m6A level changes between control and Alkbh5 knockout oocyte at GV stage

ORGANISM(S): Mus musculus

PROVIDER: GSE229771 | GEO | 2023/09/26

REPOSITORIES: GEO

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The role of ALKBH5 in maternal RNA decay during mammalian oocyte meiosis [RNA-seq]

Project description:To investigate the function of ALKBH5 in the regulation of maternal RNA decay during mice oocyte meiosis, we established Alkbh5 knockout mice and analyzed the transcriptome changes between control and Alkbh5 knockout oocyte at different meiotic maturation stages

2023-09-26 | GSE229774 | GEO

Dynamic mRNA Degradome Analyses Indicate a Role of Histone H3K4 Trimethylation in Association with Meiosis-coupled mRNA Decay in Oocyte Aging

Project description:A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrate a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance was also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) was high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, caused ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes.

2022-05-04 | GSE173598 | GEO

Single cell RNA-seq reveals mRNAs and lncRNAs important for oocyte meiosis and maturation in pigs

Project description:The faithful execution of molecular program underlying oocyte maturation and meiosis is vital to generate competent haploid gametes for effective reproduction in mammals. However, the organization and principle of gene modules and molecular circuits for oocyte meiosis remain obscure. Here, we employed the recently developed single cell RNA-seq technique to profile the transcriptomes of germinal vesicle (GV) and metaphase II (MII) oocytes, aiming to discover the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) during oocyte meiotic maturation. During the transition from GV to MII, total number of RNAs (mRNAs and lncRNAs) in oocytes decreased. Moreover, 1807 (602 up- and 1205 down-regulated) mRNAs and 313 (177 up- and 136 down-regulated) lncRNAs were significantly differentially expressed. During meiotic maturation, expression level of most mRNAs decreased, but mitochondrial RNAs, and also more lncRNAs and their target genes increased. Both DE mRNAs and lncRNAs were enriched in multiple biological and signal pathways potentially associated with oocyte meiosis. Highly abundantly expressed mRNAs (including DNMT1, UHRF2, PCNA, ARMC1, BTG4, ASNS and SEP11) and lncRNAs were also discovered. Weighted gene co-expression network analysis (WGCNA) revealed 20 hub mRNAs, and three modules of contrasting functions in oocyte maturation and meiosis. Taken together, our findings provide insights and resources for further functional investigation of mRNAs/lncRNAs in mammalian oocyte meiosis and maturation.

2021-07-19 | GSE160334 | GEO

ALKBH5 is a New Mammalian RNA Demethylase

Project description:N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as a new mammalian demethylase that oxidatively removes the m6A modification in mRNA in vitro and inside cells. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1552 differentially expressed genes which cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. We show that Alkbh5-deficiency impacts the expression levels of some of these mRNAs, supporting the observed phenotype. The discovery of this new RNA demethylase strongly suggests that the reversible m6A modification plays fundamental and broad functions in mammalian cells. RNA-seq in two cell types

2013-02-15 | E-GEOD-40132 | biostudies-arrayexpress

Chromatin state maintains human myeloid leukemia by regulating m6A demethylase ALKBH5 expression [Slam-seq]

Project description:ALKBH5 is the RNA N(6)-methyladenosine (m6A) demethylase. To understhand the function and mechnism of ALKBH5 in human acute myeloid leukemia, we compared the RNA decay rate in wild-type and ALKBH5-knock-down THP1 cells.

2020-05-27 | GSE146874 | GEO

CNOT6L Couples the Selective Degradation of Maternal Transcriptsto Meiotic Cell Cycle Progression in Mouse Oocyte [polysome RNA-seq]

Project description:Purpose: The goals of this study are to study the function of Cnot6l during oocyte maturation . Methods: Comparing the polysome-bounded transcripts at GV, MI and MII stage in WT and Cnot6l-/- oocytes by RNA sequencing. Results: Using an optimized data analysis workflow, we mapped about 15 million sequence reads per sample to the mouse genome (build mm9) and identified 23236 transcripts with TopHat workflow. Conclusions: CNOT6L stimulated degradation of maternal transcriptsto oocyte meiotic maturation.

2018-11-23 | GSE118563 | GEO

Oocyte-expressed Yes-associated Protein (YAP) is a Key Activator of the Early Zygotic Genome in Mouse

Project description:We generated maternal and paternal mouse models with Yap1-deletion, and elucidated the function of maternal YAP in zygotic genome activation. RNA sequencing with 2 WT oocyte samples at GV stage, 2 YAP-/- oocyte samples at GV stage, 1 WT embryo samples at 4cell stage, 1 YAP-/- embryo samples at at 4-cell stage.

2016-02-28 | E-GEOD-74344 | biostudies-arrayexpress

BAF250a Gdf9-cre knockout mice GV and MII stage oocyte transcriptome compared with control mice.

Project description:GV and MII stage oocyte transcriptome of control and BAF250aGKO mice.

2020-09-01 | GSE144658 | GEO

RNA exosome complex protects mouse oogenesis by clearing pervasive transcripts and regulating H3K27me3

Project description:We performed mouse single oocyte RNA-seq and bulk oocyte CUT&Tag assays in the current project. In details, SMART-seq based single oocyte RNA-seq was performed at adult GV stage, GV3h stage and MII stage, using control and Dis3 oocyte-speicfic knockout (cKO) oocytes. RiboMinus-seq based single oocyte RNA-seq was performed at adult GV stage using control and Dis3 cKO oocytes, and at p20 GV stage using control, Dis3 cKO, Exosc10 cKO and Dis3/Exosc10 double cKO (dcKO) oocytes. Bulk CUT&Tag of anti-H3K27me3 was done in WT and Dis3 cKO oocytes at adult GV stage, and in WT and Dis3/Exosc10 dcKO oocytes at p20 stage. In addition, CUT&Tag of anti-RNA polymerase II (Ser2+Ser5) was performed in WT and Dis3 cKO oocytes at GV stage. All CUT&Tag experiments share the same rabbit-Igg negative control. All p20 stage oocytes were specified as p20. The non-specified GV oocytes were all adult GV oocytes.

2022-02-11 | GSE196331 | GEO

HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge [oocyte-transcriptome]

Project description:It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammal, however, the detail molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediates recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.

2019-11-17 | GSE139665 | GEO

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