Epitranscriptomic profiling of N4-acetylcytidine-related RNA acetylation in spinal dorsal horn of rat with cancer-induced bone pain
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE225571 | GEO | 2023/05/23
REPOSITORIES: GEO
Similar Datasets
Project description:Epitranscriptomic profiling of N4-acetylcytidine-related RNA acetylation in spinal dorsal horn of rat with cancer-induced bone pain
| PRJNA936419 | ENA
Project description:mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent manner. While cytidine acetylation (ac4C) within protein-coding sequences stimulates translation, ac4C within 5’UTRs impacts protein synthesis at the level of initiation. 5’UTR acetylation promotes initiation at upstream sequences, competitively inhibiting annotated start codons. Acetylation further directly impedes initiation at optimal AUG contexts: ac4C within AUG-flanking Kozak sequences reduced initiation in base-resolved transcriptome-wide HeLa results, and in vitro utilizing substrates with site-specific ac4C incorporation. Cryo-EM of mammalian 80S initiation complexes revealed ac4C in the -1-position adjacent to an AUG start codon disrupts an interaction between C and hypermodified t6A at nucleotide 37 of the initiator tRNA. These findings demonstrate the impact of RNA modifications on nucleobase function at a molecular level and introduce mRNA acetylation as a factor regulating translation in a location-specific manner.
2022-06-08 | GSE162043 | GEO
Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.
2024-08-01 | GSE253951 | GEO
Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.
2024-08-01 | GSE253953 | GEO
Project description:The dorsal horn of the spinal cord transforms incoming somatosensory information and transmits it supraspinally to generate sensory perception, including pain and itch. Recent research using mouse Cre-driver lines has implicated specific populations of dorsal horn neurons in the transmission of different types of pain. In parallel, human genome-wide association studies (GWAS) have identified dozens of loci confidently associated with the genetic predisposition to chronic pain. The ability to connect controlled experiments in rodent models with human genetic studies could provide a platform for translational research, but the cell type heterogeneity of the dorsal horn and the complex genetic architecture of chronic pain have created challenges in bridging that gap. Here, we apply a variety of single cell genomic technologies and a comparative genomic analysis to identify conserved dorsal horn neuron subtypes whose open chromatin regions show enrichment for genetic variants associated with human chronic pain phenotypes. To achieve this, we first use single nucleus RNA-Seq and fluorescence in situ hybridization in Rhesus macaque to create a more detailed map of primate dorsal horn neuron subtypes. These were integrated with publicly available human and mouse single nucleus RNA-Seq datasets to create a multi-modal cross species atlas. Then, for the mouse dorsal horn, we combined single nucleus RNA-Seq, spatial transcriptomics, and single nucleus ATAC-Seq to infer spatial and epigenomic profiles of conserved dorsal horn neuron subtypes. Finally, we compared our conserved cell-type open chromatin resource to chronic pain GWAS and found that open chromatin regions of specific dorsal horn neuron subtypes showed enrichment for a variety of human chronic pain phenotypes. Our results provide a foundation to further explore how conserved dorsal horn neuron subtypes influence the transmission of pain signals.
2024-08-01 | GSE253952 | GEO
Project description:To identify the ac4C acetylation in the human multiple meloma cells .acRIP-seq and RNA-seq experiments of human multiple myeloma cells including NAT10 overexpression and controls were conducted.
2021-11-30 | GSE155417 | GEO
Project description:Oxaliplatin-induced neuropathic pain is a common dose-limiting side effect of cancer treatment but the underlying mechanisms are largely unknown. The neuropathic pain model was established by oxaliplatin intraperitoneal administration for five consecutive days. In the present study, we performed whole genome expression microarray analysis by using spinal dorsal horn from oxaliplatin-treated and vehicle-treated rats on day 10.
2020-03-11 | GSE146739 | GEO
Project description:More researches have revealed that N4-acetylcytidine (ac4C) affected a variety of cellular and biological processes. In order to better understand the ac4C roles in biology and disease, we present an antibody-free, fluorine assisted metabolic sequencing method to detect RNA N4-acetylcytidine, called ‘FAM-seq’. We have successfully applied FAM-seq to profile ac4C landscapes in humans. By comparing with the classic ac4C antibody sequencing method, we demonstrated that FAM-seq is a convenient and specific method for transcriptome-wide detection of ac4C. This method holds promise to detect nascent RNA ac4C modifications.
2023-10-02 | GSE234988 | GEO
Project description:As rats do not develop neuropathic pain like hypersensitivity as neonates post nerve injury but do as adults we have used these arrays to help define the processes involved in this process. Rat spinal cord (ipsilateral dorsal horn) was assayed 7 days post SNI injury to the sciatic nerve relative to sham injury. Two age groups of animals were tested Neonates (P10) and Adult (8-12wks). Experiment Overall Design: Six biologically indepenedent arrays were hybridized per assay point. Dorsal horn total RNA was prepared using standard Affymetrix protocols. Affymetrix Rat Expression 230A array used.
2009-11-10 | E-GEOD-18803 | biostudies-arrayexpress
Project description:N4 acetylcytidine (ac4C) modification mainly occurs on tRNA, rRNA, and mRNA, playing an important role in the expression of genetic information. However, it is still unclear whether microRNAs have undergone ac4C modification and their potential physiological and pathological functions. In this study, we identified that NAT10/THUMPD1 acetylates primary microRNAs (pri-miRNAs) with ac4C modification. Knockdown of NAT10 suppresses and augments the expression levels of mature miRNAs and pri-miRNAs, respectively. Molecular mechanism studies found that pri-miRNA ac4C promotes the processing of pri-miRNA into precursor miRNA (pre-miRNA) by enhancing the interaction of pri-miRNA and DGCR8, thereby increasing the biogenesis of mature miRNA. Knockdown of NAT10 attenuates the oncogenic characters of lung cancer cells by regulating miRNA production in cancers. Moreover, NAT10 is highly expressed in various clinical cancers and negatively correlated with poor prognosis. Thus, our results reveal that NAT10 plays a crucial role in cancer initiation and progression by modulating pri-miRNA ac4C to affect miRNA production, which would provide an attractive therapeutic strategy for cancers.
2024-01-01 | GSE223148 | GEO