Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Study on the Mechanism of m5C Methyltransferase NSUN3 Remodeling the Glioma Immune Microenvironment by Driving Tunneling Nanotube-Mediated Mitochondrial Transfer via tRNA Modification

ABSTRACT: Glioma is characterized by an immunosuppressive tumor microenvironment (TME) that promotes immune escape and therapeutic resistance. Mitochondrial transfer mediated by tunneling nanotubes (TNTs) is critical for tumor-stroma crosstalk, yet the underlying epigenetic regulatory mechanism remains unclear. Here, we report that the RNA m5C methyltransferase NSUN3 drives TNT formation and intercellular mitochondrial transfer in glioma by catalyzing m5C modification on tRNAs. Using tRNA-specific bisulfite sequencing (tRNA-BSseq) on human glioma cells, we systematically profiled tRNA m5C methylation landscapes in NSUN3-overexpressing and control groups. We identified NSUN3-dependent m5C sites on tRNAs that modulate translation efficiency of key factors involved in TNT assembly and mitochondrial transport. Functional assays demonstrated that NSUN3-mediated tRNA m5C modification enhances TNT formation, facilitates mitochondrial transfer from stromal cells to glioma cells, and remodels the immune microenvironment by suppressing anti-tumor immunity and promoting immunosuppressive cell infiltration. Our study reveals a novel epitranscriptomic mechanism linking tRNA m5C methylation to intercellular organelle transfer and immune regulation in glioma, providing potential targets for glioma immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE330028 | GEO | 2026/05/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Study on the Mechanism of m5C Methyltransferase NSUN3 Remodeling the Glioma Immune Microenvironment by Driving Tunneling Nanotube-Mediated Mitochondrial Transfer via tRNA Modification [RNA-Seq]

Project description:Glioma is the most common and aggressive malignant tumor in the central nervous system, and its immunosuppressive microenvironment is closely associated with therapeutic resistance and poor prognosis. NSUN3, an m5C methyltransferase, catalyzes m5C modification on tRNA and regulates RNA translation and cellular metabolism. However, the role and transcriptomic mechanism of NSUN3 in remodeling the glioma immune microenvironment remain unclear. In this study, mRNA sequencing was performed on NSUN3-knockdown glioma cells and control cells to identify differentially expressed mRNAs and related signaling pathways. Total RNA was extracted, and mRNA was enriched for library construction and high-throughput sequencing. Bioinformatics analyses including quality control, read mapping, gene quantification, differential expression screening, and functional enrichment (GO, KEGG, GSEA) were conducted. We identified a series of differentially expressed mRNAs associated with tRNA modification, mitochondrial transfer, tunneling nanotube formation, and immune regulation. These mRNAs were significantly enriched in immune response, cellular metabolism, and tumor progression pathways. Our transcriptomic data provide a comprehensive resource for understanding the mechanism by which NSUN3 drives tunneling nanotube-mediated mitochondrial transfer and remodels the glioma immune microenvironment, and offer potential targets for glioma immunotherapy.

2026-05-11 | GSE330074 | GEO

Distinct NSun methylases control cytosine-5 methylation of messenger, mitochondrial and transfer RNA: implications for human diseases [miCLIP & Bisfulfite-Seq HEK293]

Project description:Aberrant post-transcriptional methylation is implicated in a wide range of human diseases, yet the specific enzymes responsible for site- and substrate-specific methylation remain largely unknown. Here, we use our recently developed catalysis-dependent RIP sequencing approach (miCLIP) and RNA bisulfite sequencing to map C5-methylcytosine (m5C) in the human transcriptome. We identified two novel m5C methylases NSun3 and NSun6, both of which have strong substrate specificity. In contrast to the previously characterized NSun2, which displays some preference to methylating transfer RNAs (tRNA), NSun6 predominantly targeted 3’ UTRs of messenger RNAs (mRNA), and NSun3 mainly methylated mitochondrial RNAs (mtRNA). Consistent with the miCLIP-predicted RNA target specificity, whole exome sequencing identified NSUN3 loss-of-function mutations in a patient presenting with combined respiratory chain complex deficiency. Functional studies of the patient fibroblast cell line revealed that loss of the NSun3 protein resulted in severe mitochondrial translation defects, which were rescued by expression of wild-type NSun3. In summary, our results reveal how highly conserved NSun m5C methylases partition their substrate specificities to remodel the sequences of particular ribonucleotide classes.

2017-02-14 | GSE66011 | GEO

Distinct NSun methylases control cytosine-5 methylation of messenger, mitochondrial and transfer RNA: implications for human diseases [Bisulfite-Seq dermal fibroblasts]

2017-02-14 | GSE66010 | GEO

Transfer RNA (tRNA) processing and RNA m5C-methylation profiles of mouse skin squamous tumours

Project description:Purpose: High-throughput RNA sequencing has accelerated discovery of the complex regulatory roles of small RNAs, such those derived from tRNAs. Also recent advances in high-throughput RNA sequencing has revealed the complex RNA modification landscape and the complex role these nucleosides modifactions have in cell signalling, stem cell biology, development and cancer. The goal of this study is to establish how m5C-tRNA methylation and tRNA-derived small RNAs can affect stem cell fucntion in cancer. Methods: four replicates of tRNAs and RNA buisulphite sequencing of wild-type (WT) and NSun2 -/- mouse skin squamous tumours were generated by deep sequencing, using Illumina HiSeq platform. Results: Our analyses reveal that inhibition of post-transcriptional cytosine-5 methylation locks stem cells in this distinct translational inhibition programme that results in tumour progression but that also sentizes cancer cells to genotoxic stress. Transfer RNA (tRNA) sequencing and RNA Bisulphite sequencing of wild-type (WT) and NSun2 -/- mouse skin squamous tumours

2016-06-16 | E-GEOD-72065 | biostudies-arrayexpress

NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation

Project description:Mitochondrial gene expression uses a non-universal genetic code in mammals. Besides reading the conventional AUG codon, mitochondrial (mt-)tRNAMet mediates incorporation of methionine on AUA and AUU codons during translation initiation and on AUA codons during elongation. We show that the RNA methyltransferase NSUN3 localises to mitochondria and interacts with mt-tRNAMet to methylate cytosine 34 (C34) at the wobble position. NSUN3 specifically recognises the anticodon stem loop (ASL) of the tRNA, explaining why a mutation that compromises ASL basepairing leads to disease. We further identify ALKBH1/ABH1 as the dioxygenase responsible for oxidising m5C34 of mt-tRNAMet to generate an f5C34 modification. In vitro codon recognition studies with mitochondrial translation factors reveal preferential utilization of m5C34 mt-tRNAMet in initiation. Depletion of either NSUN3 or ABH1 strongly affects mitochondrial translation in human cells, implying that modifications generated by both enzymes are necessary for mt-tRNAMet function. Together, our data reveal how modifications in mt-tRNAMet are generated by the sequential action of NSUN3 and ABH1, allowing the single mitochondrial tRNAMet to recognise the different codons encoding methionine. HEK293 cell lines expressing His-FLAG-tagged NSUN3 or the His-FLAG tag alone were crosslinked using UV or treated with 5-azacytidine and analysed by CRAC

2016-08-09 | E-GEOD-84664 | biostudies-arrayexpress

tRNA Over-Expression in Breast Cancer

Project description:Increased proliferation and elevated levels of protein synthesis are characteristic of transformed and tumor cells. Though components of the translation machinery are often misregulated in cancers, how tRNA plays a role in cancer cells has not been explored. We compare genome-wide tRNA expression in tumorigenic versus non-tumorigenic breast cell lines, as well as tRNA expression in breast tumors versus normal breast tissues. In tumorigenic versus non-tumorigenic cell lines, nuclear-encoded tRNAs increase by up to 3-fold and mitochondrial-encoded tRNAs increase by up to 5-fold. In tumors versus normal breast tissues, both nuclear and mitochondrial-encoded tRNAs increase by up to 10-fold. This tRNA over-expression is selective and coordinates with the properties of cognate amino acids. Nuclear- and mitochondrial-encoded tRNAs exhibit distinct expression patterns, indicating that tRNAs can be used as biomarkers for breast cancer. We analyzed tRNA expression levels in 2 non-tumorigenic breast cell lines, 6 tumorigenic breast cancer cell lines, 3 normal breast tissue samples, and 9 breast tumor samples. We used a non-tumorigenic breast cell line (MCF10A) as a reference sample in all hybridizations. All data is dye-swapped.

2010-05-22 | E-GEOD-17945 | biostudies-arrayexpress

NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation

2016-08-09 | GSE84664 | GEO

In vivo structure profiling reveals human tRNA structurome and interactions in response to stress

Project description:Transfer RNAs (tRNAs) are the most abundant RNA family in copy numbers in a cell. It not only folds into defined structures, but also has complex interaction networks in cells involving aminoacyl-tRNA synthetases, translation factors, and ribosomes. The human tRNAome is comprised of chromosomal-encoded tRNAs with a large sequence diversity, and mitochondrial-encoded tRNAs that have A/U-rich sequences and many with non-canonical tertiary interactions. How tRNA folding and interaction in a eukaryotic cell respond to stress is poorly understood. Here, we develop DM-DMS-MaPseq, which utilizes in vivo dimethyl-sulfate (DMS) chemical probing and mutational profiling (MaP) coupled with demethylase (DM) treatment in transcriptome-wide tRNA sequencing to profile tRNA structures and their cellular interactions for human chromosomal and mitochondrial-encoded tRNAs. We found that tRNAs maintain stable structures in vivo, but the in vivo DMS profiles are vastly different from in vitro, which can be explained by their interactions with cellular proteins and the ribosome. We also identify tRNA structure and interaction changes upon arsenite treatment, an oxidative stress that induces translational reprogramming, that are consistent with enhancing reductions of translation. Our results reveal variations of tRNA structurome and dynamic interactome that have functional consequences in translational regulation.

2025-03-29 | GSE262888 | GEO

Comparison of mitochondrial tRNA abundance profiling in wild type and mutant mitochondrial RNA polymerase overexpression flies.

Project description:To investigate differential mitochondrial tRNA gene expression in wild type (WT) and mutant (E423P) mitochondrial RNA polymerase (POLRMT) overexpression flies, we performed Drsophila mitochondrial tRNA-seq according to the Hydro-tRNAseq method. tRNA-seq reads were subjected to 3' - adapter filtering , 3' - adapter trimming and quality control. The tRNAs expression levels were measured by tag count. For each tRNA sequence-based profile, the mapped reads number used to estimate the expression level of each tRNA. The tRNAs expression profiling was calculated based on uniquely mapped reads and including mapped reads, respectively. We found no difference in the relative abundance of mitochondrial individual tRNAs between WT and E423P overexpression flies.

2021-01-06 | GSE164324 | GEO

MapID-based Quantitative Mapping of Chemical Modifications and Expression of Human Transfer RNA

Project description:Transfer RNAs (tRNAs) carry abundant chemical modifications, and growing evidence shows dysregulation of chemical modifications on human tRNAs causes an expanding number of diseases including cancers, diabetes, neurological diseases, and mitochondrial disorders. Sensitive and robust detection and quantification of chemical modifications are critical to discovering functionally relevant and regulatory tRNA chemical modifications. Here we report a method “MapID-tRNA-seq” deploying a recently evolved processive reverse transcriptase to map modifications in human tRNAs and MapID-based data processing pipeline for de novo modification identification and tRNA expression quantification. MapIDs refer to consolidated sequences of human tRNA genes with reduced redundancy and annotations of genetic variation sites. MapID-based data processing largely improved the accuracy of modification detection and expression quantification by tRNA-seq, which otherwise got compromised from reads mis- and multi-alignment to the highly redundant human tRNA genome. “MapID-tRNA-seq” robustly detected the occurrence and stoichiometries of N1-methyladenosines, providing insights into the function and biosynthesis of N1-methyladenosine in human tRNAs. Our data revealed unique signatures of the evolved reverse transcriptase against N1-methyladenosine and four other types of chemical modifications. “MapID-tRNA-seq” provides a generalizable platform for de novo identification and quantitation of chemical modifications in human tRNAs to elucidate their functions in biology and diseases.

2025-04-14 | GSE229667 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data