ALKBH1-Mediated Transfer RNA Demethylation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA273642 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3322593.fastq.gz | Fastqsanger.gz | |||
| SRR3322594.fastq.gz | Fastqsanger.gz | |||
| SRR3322595.fastq.gz | Fastqsanger.gz | |||
| SRR3322596.fastq.gz | Fastqsanger.gz | |||
| SRR3322597.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Transfer RNA (tRNA) is a central component of protein synthesis and cell signaling network. One salient feature of tRNA is its heavily modified status, which can critically impact its function. Here we show that mammalian ALKBH1 is a tRNA demethylase. It mediates the demethylation of N1-methyladenosine (m1A) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in their reduced partition in polysomes and their decreased usage in protein synthesis. This process is dynamic and responds to glucose availability to affect translation. Our results uncover reversible methylation of tRNA as a new regulatory mechanism of post-transcriptional gene expression.
2016-10-13 | GSE65299 | GEO
Project description:tRNA is a central component of protein synthesis and the cell signaling network. One salient feature of tRNA is its heavily modified status, which can critically impact its function. Here, we show that mammalian ALKBH1 is a tRNA demethylase. It mediates the demethylation of N1-methyladenosine (m1A) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis. This process is dynamic and responds to glucose availability to affect translation. Our results uncover reversible methylation of tRNA as a new mechanism of post-transcriptional gene expression regulation.
| S-EPMC5119773 | biostudies-literature
Project description:ALKBH7-mediated demethylation regulates mitochondrial polycistronic RNA processing
| PRJNA623501 | ENA
Project description:AlkB homolog 1 (ALKBH1) has been reported to act as a DNA 6mA demethylase to remove 6mA modificatione in ukaryotic genomes. Our previous data showed downregalted ALKBH1 in mouse and human fatty liver and increased DNA 6mA levels in mouse fatty liver. We hypothesize that ALKBH1 may be involved in hepatic lipid metabolism. To test this hypothesis, we generated liver-specific ALKBH1 knockout (Alkbh1 f/f, Albumine-cre; AKO) mice and used high-throughput RNA sequence and other assays to directly study the role of ALKBH1 during the development of hepatic steatosis.
2022-10-26 | GSE193497 | GEO
Project description:AlkB homolog 1 (ALKBH1) has been reported to act as a DNA 6mA demethylase to remove 6mA modification in eukaryotic genomes. Our previous data showed downregulated ALKBH1 in mouse and human fatty liver and increased DNA 6mA levels in mouse fatty liver. We developed liver-specific ALKBH1 knockout (AKO) mice to directly study the role of ALKBH1 mediated DNA 6mA modification during the development of hepatic steatosis. Deletion of liver ALKBH1 promoted hepatic steatosis and insulin resistance. Overexpression of ALKBH1 resulted in opposite phenotypes. To investigate the mechanism of ALKBH1 in regulating target gene expression. We performed ChIP-seq for identifying ALKBH1 binding sites on mouse hepatocytes genomes and validated its demethylase activity for DNA 6mA modification on the target genes via ChIP-qPCR assays.
2022-10-26 | GSE197185 | GEO
Project description:DNA N6-methyladenosine (6mA) in eukaryotic genomes has recently been observed in diverse species. 6mA has been reported to associate with multiple physiological processes including embryonic development and tumorigenesis, and ALKBH1 is a primary 6mA demethylase in mouse and human cells. To research the roles of 6mA and its putative regulators such as putative ALKBH1 in the homeostatic maintenance of human stem cells and their differentiated derivatives, We generated ALKBH1-deficient human embryonic stem cells (hESCs) via CRISPR/Cas9-mediated non-homologous end joining (NHEJ). We next differentiated ALKBH1+/+ and ALKBH1-/- hESCs into human mesenchymal stem cells (hMSCs) and vascular smooth muscle cells (hVSMCs). Early-onset growth arrest of ALKBH1-/- hMSCs was observed, and increased apoptosis and enhanced migration ability were observed in ALKBH1-/- hVSMCs. However, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis revealed no change in 6mA levels between ALKBH1+/+ and ALKBH1-/- hESCs, between ALKBH1+/+ and ALKBH1-/- hMSCs, and between ALKBH1+/+ and ALKBH1-/- hVSMCs, respectively. These data demonstrate that depletion of ALKBH1 exerts minimal impact on 6mA levels in hESCs and their differentiated derivatives and that ALKBH1 regulates the homeostasis of hMSCs and hVSMCs possibly in a DNA 6mA-independent manner.
2020-05-22 | GSE150936 | GEO
Project description:Epitranscriptomic RNA modifications can regulate fundamental biological processes, but we lack approaches to map modification sites and probe writer enzymes. Here we present a chemoproteomic strategy to characterize RNA 5-methylcytidine (m5C) dioxygenase enzymes in their native context based upon metabolic labeling and activity-based crosslinking with 5-ethynylcytidine (5-EC), RNA-protein enrichment, and quantitative proteomics. We profile m5C dioxygenases in human cells including ALKBH1 and TET2 and use quantitative nucleoside LC-MS to show that ALKBH1 is the major hm5C and f5C-forming enzyme in RNA, including upon polyadenylated RNA. Further, we map ALKBH1 modification sites transcriptome-wide using 5-EC-based iCLIP analysis to show that ALKBH1 oxidizes m5C in a variety of tRNA anticodon stem loops (ASL), as well as on mRNA and lncRNA, and analyze its substrate specificity using in vitro enzymatic assays. Finally, we apply pyridine borane-mediated sequencing to identify f5C sites in tRNA ASLs. Our work provides powerful chemical approaches for studying RNA m5C dioxygenases and mapping oxidative m5C modifications and reveals the existence of novel epitranscriptomic pathways for regulating RNA function.
2022-07-16 | PXD029955 | Pride
Project description:DNA 6-adenine methylation (6mA), as a novel adenine modification existing in eukaryotes, shows essential functions in embryogenesis and mitochondrial transcriptions. ALKBH1 is a demethylase of 6mA and plays critical roles in osteogenesis, tumorigenesis, and adaptation to stress. However, the integrated biological functions of ALKBH1 still require further exploration. Here, we demonstrate that knockdown of ALKBH1 inhibits adipogenic differentiation in both human mesenchymal stem cells (hMSCs) and 3T3-L1 preadipocytes, while overexpression of ALKBH1 leads to increased adipogenesis. Using a combination of RNA-seq and N6-mA-DNA-IP-seq analyses, we identify hypoxia-inducible factor-1 (HIF-1) signaling as a crucial downstream target of ALKBH1 activity. Depletion of ALKBH1 leads to hypermethylation of both HIF-1α and its downstream target GYS1. Simultaneous overexpression of HIF-1α and GYS1 restores the adipogenic commitment of ALKBH1-deficient cells. Taken together, our data indicate that ALKBH1 is indispensable for adipogenic differentiation, revealing a novel epigenetic mechanism that regulates adipogenesis.
2021-12-12 | GSE177059 | GEO
Project description:The aim of the study was to elucidate the role of Alkbh1 by targeted deletion in C57/BL6 mice. Alkb deficiency results in sex-ratio distortion of offspring and apoptosis in adult testes, most likely caused by defects in the pachytene stage during spermatogenesis. Due to the pivotal role of Alkbh1 in mouse survival and potentially in germ cells, we searched for Alkbh1-regulated genes in adult testes. Testes from 12 week old mice were selected for RNA extraction and hybridization on Affymetrix microarrays. We used testes from 3 wild type mice and 3 KO mice
2010-06-08 | E-GEOD-22073 | biostudies-arrayexpress
Project description:AlkB homolog 1 (ALKBH1) is one of nine members of the AlkB homologs in mammals. Most Alkbh1-deficient mice die during embryonic development, and survivors have severe defects in tissues originating from the ectodermal lineage. We hypothesized the phenotype to rely upon aberrant epigenetic regulation and provided evidence for ALKBH1 to be a histone H2A demethylase. We used a whole genome expression microarray to detail differentially expressed genes in embryonic stem cells lacking the Alkbh1 gene and identified distinct classes of up- and down-regulated genes during this process. Wild type and Alkbh-/- embryonic stem cells were established to identify differentially expressed genes at day 0, undifferentiated cells. We sought to obtain a subset of genes possibly explaining the observed phenotype. Total RNA was extracted and hybridized on Affymetrix GeneChips. 3 parallels were analyzed from each of the two genotypes.
2011-11-01 | E-GEOD-30561 | biostudies-arrayexpress