M6A sequences 2 WT_input vs 2 Ythdf1 KO_input
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE281731 | GEO | 2024/11/17
REPOSITORIES: GEO
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Project description:To understand the functional roles of YTHDF1 in cellular senescence and aging, we lead the RNA sequence in WT or Ythdf1 deficiency colon epithelial cells. The results showed that the cholesterol biosynthesis related genes were upregulated in Ythdf1 KO mice. We also purified FLAG-YTHDF1 protein in HEK293T cells and did protein mass spectrometry, and found that the mTORC1 and TSC complex constituents mTOR, RPTOR, and TSC1/2 were identified in the YTHDF1-complex. Methylated RNA immunoprecipitation(MeRIP) with specific m6A antibody and used for library construction and the next generation sequencing, to identify m6A modified transcripts in WT or Ythdf1 deficiency colon epithelial cells after DSS treatment
2020-05-06 | GSE149883 | GEO
Project description:N6-methyladenosine (m6A) RNA methylation is implicated in the progression of multiple cancers via influencing mRNA modification. Intersection of RNA-seq, Methylated RNA immune-precipitation (MeRIP)-seq, co-immunoprecipitation, RNA pull-down and MeRIP-PCR were used to identify YTHDF1- modified USP14 and its m6A levels in GC cells. Intersection assays revealed that YTHDF1 promoted USP14 protein translation in an m6A-dependent manner. Our data suggested that m6A reader YTHDF1 facilitated tumorigenesis and metastasis of GC by promoting USP14 protein translation and might act as a clinical therapy for GC.
2021-04-07 | GSE166972 | GEO
Project description:WTAP is an essential component of the RNA N-6-methyladenosine (m6A) modification complexes that guides METLL3-METLL14 heteroduplexes to target RNAs in the nucleus of mammalian cells. Through mining the genotype-tissue expression (GTEx) datasets, we initially found that TTC22 expression was highly correlated with WTAP and FTO in many normal human tissues. Our experimental results indicate that TTC22 could directly capture RNA binding protein RPL4, induce the binding between RPL4 and WTAP mRNA in the cytoplasm, which increased the m6A level, induced alterative splicing, enhanced the stability and translation efficiency of WTAP mRNA, and consequently upregulated the level of total m6A RNA. These results indicate that WTAP mRNA is a m6A target and there is a positive feedback loop between total m6A and WTAP expression. YTHDF1 was found to be an essential m6A WTAP mRNA binding protein. Downregulation of RPL4, WTAP, or YTHDF1 expression could reverse TTC22-enhanced total m6A RNA level. m6A-specific antibody immunoprecipitated RNA-sequencing (meRIP-seq) demonstrated that TTC22 caused dramatic expression changes of genes related to metabolic pathways, ribosome biogenesis, and RNA spliceosome. Furthermore, we also found that TTC22 upregulated the expression of epithelial-mesenchymal transition (EMT)-related gene SNAI1 via m6A, and promoted metastasis of colon cancer in vitro and in mice. In conclusion, our study illustrates that WTAP mRNA is a m6A target using YTHDF1 as the binding protein. TTC22 could upregulate the levels of WTAP expression and total m6A RNA through the PRL4 binding. The m6A-mediated upregulation of SNAI1 expression may contribute to TTC22-enhanced colon cancer metastasis.
2024-11-10 | GSE188521 | GEO
Project description:The N6-methyladenosine (m6A) mRNA modification and the mitochondrial respiratory chain (MRC) hold paramount importance in the advancement of MASLD. This study thoroughly investigates the relationship and impact of m6A mRNA modification and mitochondrial function in the progression of MASLD. Here we report that the mRNA and protein levels of mitochondrial respiratory chain (MRC) subunits showed inconsistent trends in vivo experiments. Abnormal m6A modification and mitochondrial dysfunction in MASLD were attributed to the upregulation of methyltransferase like 3 (Mettl3) and the downregulation of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) induced by high-fat foods. Mettl3 promoted the MRC's function. However, knockout of the reader protein YTHDF1, which plays a crucial role in the m6A modification process, counteracted the effect of Mettl3 and suppressed MRC. In MASLD, damage to the MRC may be regulated by the Mettl3-m6A-YTHDF1 complex axis, especially by the role of YTHDF1. Our research has offered a novel perspective on the involvement of m6A mRNA methylation in the pathogenesis of MASLD.
2024-09-20 | PXD047819 | Pride
Project description:N6-methyladenosine (m6A) is the most prevalent internal RNA modification in mammalian messenger RNAs (mRNAs). While m6A has been shown to mark groups of mRNAs for coordinated degradation in various physiological processes, the relevance of m6A in affecting translation remains to be determined in intact biological systems in vivo. Here we show that, through its reader protein Ythdf1, m6A promotes a pulse of protein synthesis of target transcripts in response to neuronal stimuli in the adult mouse hippocampus, thereby facilitating learning and memory processes. Mice with genetic deletion of the Ythdf1 gene (Ythdf1-/-) exhibit learning and memory defects, as well as impaired hippocampal synaptic transmission and long-term potentiation (LTP). Selective re-expression of Ythdf1 in the hippocampus of adult Ythdf1-/- mice fully rescues the behavioral and synaptic defects, while hippocampus-specific knockdown of Ythdf1 or Mettl3, the catalytic component of m6A methyltransferase complex, recapitulates the hippocampal deficiency in adult mice. At the molecular level, transcriptome-wide mapping of m6A sites and RNA binding sites of Ythdf1 on hippocampal mRNAs using crosslinking immunoprecipitation followed by high-throughput sequencing (CLIP-seq) uncovered key neuronal genes, including those involved in synaptic transmission and long-term potentiation. Nascent protein labelling and tether reporter assays in cultured hippocampal neurons revealed that Ythdf1 is critical for initiating a pulse of protein synthesis of target transcripts in a neuronal-stimulus-dependent manner. Collectively, our results uncover a pathway of mRNA m6A methylation in learning and memory, which is mediated through Ythdf1 in response to stimuli.
2018-08-17 | GSE106607 | GEO
Project description:The human YTH domain family protein (YTHDF) family is RNA binding protein which specifically recognizes N6-methyladenosine (m6A), and exerts distinct roles in eukaryocytes; YTHDF1 promotes the translation of m6A modified mRNAs collaborating with initiation factors, and YTHDF2 reduces the stability of the m6A-modified transcripts. We used the Nanostring nCounter to detail the differential gene expression by YTHDF1 and YTHDF2.
2021-08-24 | GSE171634 | GEO
Project description:m6A sequences 2 WT_input vs 2 Ythdf1 KO_input
| PRJNA1185384 | ENA
Project description:N6-methyladenosine (m6A), the most abundant modification in mRNAs, has been defined as a crucial modulator in the progression of acute myeloid leukemia (AML), while the detailed mechanism remains elusive. Here we report that YTHDF1, an m6A reader protein, is overexpressed in human AML samples with enrichment in leukemia stem cells (LSCs). Whereas YTHDF1 is dispensable for normal hematopoiesis in mice, depletion of YTHDF1 attenuates self-renewal and proliferation of patient-derived LSCs, and impedes leukemia establishment in immunodeficient mice. Mechanistically, YTHDF1 promotes the translation of diverse m6A-modified oncogene mRNAs particularly cyclin E2. We applied a structure-based virtual screening of FDA-approved drugs and identified tegaserod as a potential YTHDF1 inhibitor. Tegaserod blocks the direct binding of YTHDF1 with m6A-modified mRNAs and inhibits YTHDF1-regulated mRNA translation. Moreover, tegaserod inhibits leukemogenesis in vitro and in mice, phenocopying the loss of YTHDF1. Together, our study defines YTHDF1 as an integral regulator of AML progression at the translational level and identifies tegaserod as a potential therapeutic agent for AML by targeting YTHDF1.
2021-09-28 | GSE184842 | GEO
Project description:In addition to perform the m6A-seq in A549 cells, we sequenced RNA obtained from the immuno-purified complex of YTHDF1 (RIP-seq) to reveal YTHDF1 bound mRNAs, 3,676 genes were shared (m6A-seq+RIP-seq) as high-confident targets of YTHDF1 , which were mapped to cell cycle and tumor (including lung cancer) related signaling pathways in the KEGG pathway database
2019-09-26 | GSE136433 | GEO
Project description:m6A and YTHDF1, YTHDF2, YTHDF3 mapping of IAV RNA with PAR-CLIP and pA-m6A-seq
2017-10-17 | GSE98033 | GEO