RNA-seq to profile the alterations in transcript half-lives regarding to ac4C regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE226751 | GEO | 2023/08/25
REPOSITORIES: GEO
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Project description:NAT10-catalyzed N4-acetylcytidine (ac4C) has emerged as a vital post-transcriptional modulator on the coding transcriptome by promoting mRNA stability. To investigate the effect of NAT10-mediated ac4C acetylation modification on gene expression level, we performed high throughput RNA sequencing experiments of control and NAT10 KD hESCs each with 4 replicates.
2023-08-25 | GSE226749 | GEO
Project description:NAT10-catalyzed N4-acetylcytidine (ac4C) has emerged as a vital post-transcriptional modulator on the coding transcriptome by promoting mRNA stability. To explore the transcriptome-wide profile of ac4C modification, we mapped the locations of ac4C modification on wild-type (WT) hESCs and NAT10 KD hESCs by NaCNBH3-based chemical ac4C sequencing (ac4C-seq).
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Project description:NAT10-catalyzed N4-acetylcytidine (ac4C) has emerged as a vital post-transcriptional modulator on the coding transcriptome by promoting mRNA stability. To explore the transcriptome-wide profile of ac4C modification, we mapped the locations of ac4C modification on wild-type (WT) hESCs and NAT10 KD hESCs by high-throughput ac4C RNA immunoprecipitation sequencing (ac4C-RIP-seq).
2023-08-25 | GSE226748 | GEO
Project description:N4-acetylcytidine (ac4C), a conserved chemical modification in eukaryotic prokaryotes that is catalyzed by the N-acetyltransferase 10 (NAT10) enzyme, plays a crucial role in promoting mRNA stability and translation. However, the biological function and mechanisms of NAT10-mediated ac4C in human cancer were poorly defined. In order to investigate the regulatory mechanism of NAT10 in gastric cancer, we performed ac4C RIP-seq(acRIP-seq) analysis in AGS cells with NAT10 knockout compared with control in two repeats.
2024-07-07 | GSE180494 | GEO
Project description:R-loop remodeling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer to sustain self-renewal and malignancy remains poorly understood. Here, we found that glioblastoma (GBM) stem cells (GSCs) display highly active R-loops compared to differentiated tumor progeny and neural stem cells (NSCs). Genome-wide mapping by R-loop RNA chromatin immunoprecipitation sequencing (RR-ChIP-seq) revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. We profiled R-loop interactomes and identified N-Acetyltransferase 10 (NAT10), an RNA N4-acetylcytidine (ac4C)-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 was overexpressed in GSCs. ac4C-specific RNA immunoprecipitation sequencing (ac4C-RIP-seq) on R-loop RNA revealed genome-wide mapping of ac4C-modified R-loops with abundant ac4C-modified R-loops that regulated the genome. NAT10 catalyzed widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating open chromatin to sustain self-renewal through core stemness regulators, including transcription factor EGR1. NAT10 knockdown suppressed proliferation and maintenance in vitro and attenuated tumor growth in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting cancer.
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Project description:Vascular smooth muscle cells (VSMCs) phenotype switching is a pathological hallmark in various cardiovascular diseases. N4-acetylcytidine (ac4C), catalyzed by N-acetyltransferase 10 (NAT10), is well conserved in the enzymatic modification of RNA. NAT10-mediated ac4C acetylation is involved in various physiological and pathological processes, including cardiac remodeling. However, the biological functions and underlying regulatory mechanisms of mRNA ac4C modifications in vascular diseases remain elusive. By combining in vitro and in vivo vascular injury models, we identified NAT10 as a crucial protein involved in the promotion of postinjury neointima formation as well as VSMCs proliferation. The potential mechanisms of NAT10 in vascular neointima formation were clarified by RNA sequence (RNA-seq), acetylated mRNA immunoprecipitation sequence (acRIP-seq), and RNA binding protein immunoprecipitation sequence (RIP-seq). NAT10 and ac4C modification were upregulated in injured human and rodent arteries. Deletion of NAT10 in VSMCs effectively reduces postinjury neointima formation and VSMCs phenotype switching. Further RNA-seq, RIP-seq, and acRIP-seq revealed that NAT10, by its ac4C modification, directly interacts with genes, including integrin-β1 (ITGB1) and collagen type I alpha 2 chain (Col1a2) mRNAs. NAT10-mediated ac4C consequently increased ITGB1 mRNA stability and its downstream focal adhesion kinase (FAK) signaling, thereby directly influencing the proliferation of VSMCs and vascular remodeling. The regulation of NAT10 on VSMC phenotype is of translational significance because administration of remodelin, a NAT10 inhibitor, effectively prevents neointima formation by suppressing VSMCs proliferation and downregulating of ITGB1 expression and deactivating its FAK signaling. Our study reveals that NAT10 promotes vascular remodeling via mRNA Ac4c acetylation, which may be a promising therapeutic target against vascular remodeling.
2026-07-20 | GSE272001 | GEO
Project description:Pancreatic cancer is a lethal diease with high tendency of metastasis. Howerver, the mechanisms of pancreatic cancer are sitill unclear. To explore the roles of N4-acetylation (ac4C) RNA modification and its involved N-Acetyltransferase 10 (NAT10) in pancreatic ductal adenocarcinoma (PDAC), we performed profiling by high throughput sequencing. In this study, we investigate the effects of NAT10 knockdown on N4-acetylcytidine (ac4C) modification in mRNA within PANC-1 cells using ac4C-seq. By employing RNA interference to specifically knock down NAT10 expression in PANC-1 cells, we aim to elucidate its impact on ac4C RNA modifications, which have been implicated in various cellular processes and cancer progression. Total RNA was extracted and mRNA was captured and treated with sodium borohydride (NaBH4) for detection of ac4C sites.Following library preparation, sequencing was performed on an Illumina Novaseq 6000 platform. Bioinformatics analyses identified significant changes in ac4C modification patterns due to NAT10 depletion. This dataset provides a valuable resource for further exploration of ac4C modifications in mRNA and their role in PDAC.
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Project description:N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification is crucial for mRNA stability and translation efficiency, yet the underlying function in mammalian preimplantation embryos remains unclear.
2023-07-17 | GSE236943 | GEO
Project description:Programmed establishment of the zygote epitranscriptome orchestrates epitranscriptome fidelity and developmental potency acquisition during mammalian preimplantation embryogenesis. N4-acetylcytidine (ac4C) is a conserved post-transcriptional RNA modification catalyzed by the only known “writer”, N-acetyltransferase 10 (NAT10), but its landscape and function in early embryos remain further exploration owing to limited materials. In this study, we characterized the ac4C modification reprogramming dynamics throughout preimplantation embryogenesis and identified that Nat10 ablation from primary follicle oocytes leads to female infertility with embryonic arrest at the 2-cell transition. Notably, we found that the maternal protein NAT10 was essential for ac4C deposition on ZGA transcripts and maternal mRNAs, and the loss of Nat10 could also lead to abnormal accumulation of maternal transcripts and major ZGA inactivation. Interestingly, through combinatorial interrogation of RNA-seq and ribo-seq data, we uncovered NAT10 regulates the alternative splicing of transcripts that function during zygotic splicing activation in an ac4C-dependent manner. In summary, our findings demonstrate that the RNA ac4C writer NAT10 is essential for the post-transcriptional regulation of mouse zygotic splicing activation and provide valuable view for further exploration of the epigenetic mechanism during maternal-to-zygotic transition.
2026-08-11 | GSE308284 | GEO
Project description:Programmed establishment of the zygote epitranscriptome orchestrates epitranscriptome fidelity and developmental potency acquisition during mammalian preimplantation embryogenesis. N4-acetylcytidine (ac4C) is a conserved post-transcriptional RNA modification catalyzed by the only known “writer”, N-acetyltransferase 10 (NAT10), but its landscape and function in early embryos remain further exploration owing to limited materials. In this study, we characterized the ac4C modification reprogramming dynamics throughout preimplantation embryogenesis and identified that Nat10 ablation from primary follicle oocytes leads to female infertility with embryonic arrest at the 2-cell transition. Notably, we found that the maternal protein NAT10 was essential for ac4C deposition on ZGA transcripts and maternal mRNAs, and the loss of Nat10 could also lead to abnormal accumulation of maternal transcripts and major ZGA inactivation. Interestingly, through combinatorial interrogation of RNA-seq and ribo-seq data, we uncovered NAT10 regulates the alternative splicing of transcripts that function during zygotic splicing activation in an ac4C-dependent manner. In summary, our findings demonstrate that the RNA ac4C writer NAT10 is essential for the post-transcriptional regulation of mouse zygotic splicing activation and provide valuable view for further exploration of the epigenetic mechanism during maternal-to-zygotic transition.
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