Similar Datasets
Project description:YTHDC2 CLIP and RNA-seq and Ribo-seq of Ythdc2KO and Ythdc2-WLA mutants
| PRJNA789243 | ENA
Project description:N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA. It is dynamically installed and removed, and acts as an essential layer of mRNA metabolism, regulating biological processes including stem cell pluripotency, cell differentiation, and energy homeostasis. m6A is recognized by selective binding proteins; YTHDF1 and YTHDF3 work in concert to promote the translation of m6A-containing mRNAs, YTHDF2 expedites mRNA decay, and YTHDC1 affects the splicing of its targets. The biological function of YTHDC2, the final member of the YTH protein family, remains unknown. We report that YTHDC2 selectively binds m6A along its consensus motif GGACU. YTHDC2 promotes translation of its targets, and associates with cellular fractions involved in translation initiation. Ythdc2 knockout mice are infertile and have significantly smaller testes compared to those of littermates. In the testes, Ythdc2 is temporally expressed as meiosis begins, and germ cells of Ythdc2 knockout mice do not develop past the spermatogonium stage. Thus, YTHDC2 is an m6A binding protein that plays essential roles in spermatogenesis.
2017-08-01 | GSE98085 | GEO
Project description:Mouse cortex or cerebellum samples from E18.5 or P28 Nova2-cTag mouse crossed with a series of Cre driver mice were subjected to Nova2 cTag-CLIP to generate functional NOVA2-RNA maps from single neuronal populations in the mouse brain.
2019-01-09 | GSE103315 | GEO
Project description:In the germline stem cell lineage, proliferating gonial cells switch from mitotic proliferation to meiotic prophase, marked by the onset of a cell-type-specific transcription program and a specialized cell cycle required to generate haploid gametes. The Drosophila gene benign gonial cell neoplasm (bgcn) encodes an RNA binding translational repressor required in fly testes for spermatogonia to stop dividing and transition to the spermatocyte state and meiosis. Here we show that the mammalian bgcn ortholog, YTHDC2, plays a key role in allowing a clean transition from mitosis to meiosis in both male and female germ cells in mouse, pointing towards a conserved role of post-transcriptional control of RNA translation and/or stability in this critical cell fate transition. Ythdc2-/- male germ cells undergo mitotic divisions but fail to properly execute meiotic prophase, instead attempting a mitotic-like division then undergoing cell death. Many meiotic markers were only weakly expressed in Ythdc2-/- testes compared to wild-type controls. Strikingly, the mitotic cyclin Cyclin A2, which is down-regulated prior to entry into meiotic prophase in wild-type, remained high in Ythdc2-/- germ cells that also expressed the meiotic marker SYCP3, suggesting that the mutant germ cells attempting to enter meiotic prophase have a mixed identity. YTHDC2 binds RNAs involved in both the mitotic cell cycle, including the mRNA Ccna2 that encodes Cyclin A2, as well as specific piRNA precursor RNAs and transcripts required for later stages of germ cell differentiation. YTHDC2-bound RNAs in testes were enriched for the m6A modification, suggesting that YTHDC2 may selectively regulate multiple target RNAs marked with m6A, to promote a clean transition from mitosis to meiosis and terminal differentiation.
2017-11-15 | GSE93566 | GEO
Project description:In the germline stem cell lineage, proliferating gonial cells switch from mitotic proliferation to meiotic prophase, marked by the onset of a cell-type-specific transcription program and a specialized cell cycle required to generate haploid gametes. The Drosophila gene benign gonial cell neoplasm (bgcn) encodes an RNA binding translational repressor required in fly testes for spermatogonia to stop dividing and transition to the spermatocyte state and meiosis. Here we show that the mammalian bgcn ortholog, YTHDC2, plays a key role in allowing a clean transition from mitosis to meiosis in both male and female germ cells in mouse, pointing towards a conserved role of post-transcriptional control of RNA translation and/or stability in this critical cell fate transition. Ythdc2-/- male germ cells undergo mitotic divisions but fail to properly execute meiotic prophase, instead attempting a mitotic-like division then undergoing cell death. Many meiotic markers were only weakly expressed in Ythdc2-/- testes compared to wild-type controls. Strikingly, the mitotic cyclin Cyclin A2, which is down-regulated prior to entry into meiotic prophase in wild-type, remained high in Ythdc2-/- germ cells that also expressed the meiotic marker SYCP3, suggesting that the mutant germ cells attempting to enter meiotic prophase have a mixed identity. YTHDC2 binds RNAs involved in both the mitotic cell cycle, including the mRNA Ccna2 that encodes Cyclin A2, as well as specific piRNA precursor RNAs and transcripts required for later stages of germ cell differentiation. YTHDC2-bound RNAs in testes were enriched for the m6A modification, suggesting that YTHDC2 may selectively regulate multiple target RNAs marked with m6A, to promote a clean transition from mitosis to meiosis and terminal differentiation.
2017-11-15 | GSE93533 | GEO
Project description:In order to identify YTHDC2 downstream genes, we performed RNA-seq in WT and YTHDC2 knockout H1975 cells and analyzed the changed mRNAs.
2023-08-29 | GSE241622 | GEO
Project description:Mouse samples were subjected to HITS-CLIP to monitor Elavl binding
2019-09-30 | GSE104025 | GEO
Project description:We report the differentially expressed genes caused by inducible deletion of YTHDC2 in pachytene spermatocytes. A large number of differentially epxressed genes were identified.
2022-01-11 | GSE166568 | GEO
Project description:N6-methyladenosine (m6A) is an essential internal RNA modification that is critical for gene expression control in most organisms. Proteins with a YTH domain recognize m6A marks and are mediators of molecular functions like RNA splicing, mRNA decay and translation control. Here we demonstrate that YTH domain-containing 2 (YTHDC2) is an m6A reader that is essential for male and female fertility in mice. In mutant males, mitotic spermatogonia fail to differentiate into meiotic spermatocytes. Analysis identifies transcripts upregulated in the Yhtdc2 mutant testes to be those that are expressed in purified spermatogonia, while high-throughput mapping of the m6A transcriptome in the mouse male germline demonstrates the upregulated transcripts to be those that are enriched in m6A marks. Our biochemical studies indicate that YTHDC2 is an RNAinduced ATPase that fuels its 3ʹ→5ʹ RNA helicase activity. Interestingly, we find an RNA-independent interaction between the 5ʹ→3ʹ exoribonuclease XRN1 and the Ankyrin repeat of YTHDC2 that is wedged in between the two RecA helicase domains. Our studies reveal a role for YTHDC2 in modulating the levels of m6A-modified germline transcripts that is essential for successful meiosis.
2017-10-14 | GSE102346 | GEO