The role of ALKBH5 in maternal RNA decay during mammalian oocyte meiosis
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ABSTRACT:
PROVIDER: PRJNA955804 | ENA |
REPOSITORIES: ENA
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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 m6A level changes between control and Alkbh5 knockout oocyte at GV stage
2023-09-26 | GSE229771 | GEO
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
Project description:The role of ALKBH5 in maternal RNA decay during mammalian oocyte meiosis [RNA-seq]
| PRJNA955806 | ENA
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
Project description:Oocyte meiosis is an important factor affecting female reproduction. Breast cancer amplified sequence 2 (BCAS2) is a component of the spliceosome. Previous reports have shown that BCAS2 is critical in male germ cell meiosis, oocyte development, and early embryo genome integrity. However, the role of BCAS2 in oocyte meiosis has not been reported. We used Stra8-GFP-Cre mice to knock out BCAS2 during the pachytene phase of oocytes. The results of fertility tests showed that the cko mice were infertile. Morphological analysis showed that the number of primary follicles of 2M ovary was significantly reduced and follicle development was blocked. Further analysis showed that the number of primordial follicles decreased and follicle development slowed from 7dpp ovaries. Sequencing revealed that DNA damage in oocytes could not be repaired from 5dpp. There was an abnormality in meiosis, some oocytes could not reach the diplotene stage of meiosis, and more oocytes could not develop to the dictyate stage. AS analysis reveals that abnormal variable splicing of Dazl and Diaph2 Oogens-related genes in cKO mice, with involvement of the PRP19/CDC5l complex.
2024-01-01 | GSE228983 | GEO
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
Project description:During Caenorhabditis elegans oocyte meiosis, a multi-protein complex localised between homologous chromosomes, the ring complex (RC), promotes chromosome congression through the action of the chromokinesin KLP-19. While some RC components are known, the mechanism of RC assembly has remained obscure. A germline-specific screen identified KLP-19 as a SUMO substrate in vivo and we found that the SUMO E3 ligase GEI-17/PIAS is required for KLP-19 recruitment to the RC. Additionally, KLP-19 is efficiently sumoylated in vitro in a GEI-17-dependent manner. Further biochemical analysis showed that KLP-19 and GEI-17 are efficiently modified by SUMO and that GEI-17 and another RC component, the kinase BUB-1, can interact non-covalently with SUMO. While SUMO conjugation is required for RC assembly, we also provide evidence consistent with non-covalent SUMO interactions contributing to RC assembly in vivo. Our results highlight the importance of sumoylation and non-covalent SUMO interaction in regulating dynamic protein complex assembly during oocyte meiosis.
2020-10-15 | PXD005202 | Pride
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
Project description:Maternal RNAs are stored from minutes to decades in oocytes throughout meiotic arrest. The nature and dynamics of maternal RNAs during this arrest remain uncharted. We address this by performing single-oocyte RNA sequencing on arrested and maturing C. elegans oocytes. We discovered a population of transcripts that increases as the arrested meiosis I oocyte ages, but ruled out ERK signaling and nascent transcription as a mechanism for this increase. Instead, we report extracellular communication from neighboring somatic cells as a mechanism for the increase in transcripts during meiosis I arrest. These analyses provide a single-cell resolution of the RNA landscape during the developmental history of a meiosis I arrested oocyte and as it prepares for oocyte maturation and embryonic progression.
2023-05-24 | GSE209988 | GEO
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