Direct RNA sequencing of mouse and human rRNA
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ABSTRACT:
PROVIDER: PRJEB81662 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epitranscriptomic rRNA fingerprinting reveals tissue-of-origin and tumor-specific signatures
| PRJNA1103776 | ENA
Project description:Mammalian ribosomal RNA (rRNA) molecules are highly abundant RNAs, decorated with over 220 different rRNA modifications, changing their chemical and biological properties. Previous works have shown that some types of rRNA modifications can be dynamically regulated; however, a comprehensive analysis of how the mammalian rRNA modification landscape is remodeled across time, cell types and upon disease conditions, remains largely unexplored. Here, we employ direct RNA nanopore sequencing to generate maps of human and mouse rRNA modifications across tissues, developmental stages, cell types and disease conditions. Our analyses reveal multiple rRNA sites that are differentially modified in a tissue- and/or developmental stage-specific manner. Notably, the adult brain exhibits the most distinct rRNA modification patterns, including previously unannotated rRNA modified sites. We then demonstrate that dynamic rRNA modification patterns can be used for tissue and cell type identification, which we hereby term ‘epitranscriptomic fingerprinting’. We then explored rRNA modification patterns in normal-tumor matched samples from lung cancer patients, finding that rRNA epitranscriptomic fingerprinting accurately classified clinical samples into normal and tumor groups from only 250 reads per sample, demonstrating the potential of rRNA modifications as diagnostic biomarkers, and revealing rRNA modifications as a rich source of information for tissue, cell type and disease identification.
2024-11-28 | GSE264668 | GEO
Project description:Mammalian ribosomal RNA (rRNA) molecules are highly abundant RNAs, decorated with over 220 different rRNA modifications, changing their chemical and biological properties. Previous works have shown that some types of rRNA modifications can be dynamically regulated; however, a comprehensive analysis of how the mammalian rRNA modification landscape is remodeled across time, cell types and upon disease conditions, remains largely unexplored. Here, we employ direct RNA nanopore sequencing to generate maps of human and mouse rRNA modifications across tissues, developmental stages, cell types and disease conditions. Our analyses reveal multiple rRNA sites that are differentially modified in a tissue- and/or developmental stage-specific manner. Notably, the adult brain exhibits the most distinct rRNA modification patterns, including previously unannotated rRNA modified sites. We then demonstrate that dynamic rRNA modification patterns can be used for tissue and cell type identification, which we hereby term ‘epitranscriptomic fingerprinting’. We then explored rRNA modification patterns in normal-tumor matched samples from lung cancer patients, finding that rRNA epitranscriptomic fingerprinting accurately classified clinical samples into normal and tumor groups from only 250 reads per sample, demonstrating the potential of rRNA modifications as diagnostic biomarkers, and revealing rRNA modifications as a rich source of information for tissue, cell type and disease identification.
2024-11-28 | GSE280137 | GEO
Project description:Eukaryotic ribosomal RNA carries diverse posttranscriptional modifications, among which the evolutionarily conserved 2’-O-methylation (2’-O-Me) occurs at more than 100 sites and is essential for ribosome biogenesis. Plasticity of 2´-O-Me in ribosomes and its functional consequences in human disease are not yet known. Here, we present the full rRNA 2’-O-Me landscape (ribomethylome) of human acute myeloid leukemia (AML) through profiling 94 patient samples as well as 21 normal hematopoietic samples of 5 different lineages. While interior modification sites in functional centers are persistently fully 2’-O-methylated in human AMLs, methylation on ribosome exterior sites is unprecedentedly dynamic. Higher 2’-O-methylation on exterior dynamic sites is associated with leukemia stem cell (LSC) signatures. Forced expression of enzymatically active but not of the catalytic defect 2’-O-methyltransferase FBL induces AML stemness and accelerates leukemogenesis in patient-derived xenografts. Mechanistically, ribomethylome dynamics shifted mRNA ribosome translation preferences. High rRNA 2’-O-Me enhances translation of amino acid transporters enriched in optimal codons and subsequently increases intra-cellular amino acid levels. Methylation on a single exterior modification site affects leukemia stem cell activity. The Guanosine 1447 on the small subunit ribosomal RNA is the most variable site in primary AMLs. Gm1447 is increased in leukemia stem cell populations compared to non-leukemogenic blast cells and AML specimens with higher Gm1447 are enriched for leukemia stem cell genes. Comparison of Gm1447high and Gm1447low ribosome structure solved by cryo-electron microscopy demonstrated disassociation of LYAR from Gm1447low ribosomes. Suppression of Gm1447 alone is sufficient to suppress translation of amino acid transporters, resulting in decreased cellular amino acid levels and leukemia stem cell activity. Taken together, our data reveal the dynamic FBL-mediated rRNA 2'-O-Me landscape as a novel epitranscriptomic level of control employed by leukemic stem cells and may enable new strategies to target human AML.
2023-03-11 | PXD029527 | Pride
Project description:Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/- mice and cells, both of which exhibited dramatic mitochondrial changes. Subsequently, WBSCR16 was identified as a 16S rRNA-binding protein essential for the cleavage of 16S rRNA-mt-tRNALeu, facilitating 16S rRNA processing and mitochondrial ribosome assembly. Additionally, WBSCR16 recruited RNase P subunit MRPP3 to nascent 16S rRNA and assisted in this specific cleavage. Furthermore, evidence showed that adipose-specific Wbscr16 ablation promotes energy wasting via lipid preference in brown adipose tissue, leading to excess energy expenditure and resistance to obesity. In contrast, overexpression of WBSCR16 upregulated 16S rRNA processing and induced a preference for glucose utilization in both transgenic mouse models and cultured cells. These findings suggest that WBSCR16 plays essential roles in mitochondrial 16S rRNA processing in mammals, and is the key mitochondrial protein to balance glucose and lipid metabolism.
2024-12-30 | GSE229693 | GEO
Project description:DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.
2023-03-02 | GSE210208 | GEO
Project description:DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.
2023-03-02 | GSE210293 | GEO
Project description:DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.
2023-03-02 | GSE210211 | GEO
Project description:DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.
2023-03-02 | GSE210210 | GEO