Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [array]
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ABSTRACT:
PROVIDER: PRJNA1035125 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:RNA modifications, including m6A, critically modulate protein expression program in a range of cellular processes. Although cellular senescence has been linked to age-related diseases and functional declines, the landscape and impact of m6A modification are poorly understood. Here, we report a robust m6A modification of Patched-Domain Containing Protein 4 (PTCHD4) mRNA at m6A in senescent cells. The METTL3/METTL14 complex was found to mediate the m6A modification of PTCHD4 mRNA, which increased PTCHD4 mRNA stability and PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as being responsible for stabilization and increased abundance of PTCHD4 mRNA by m6A modification. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells, and sensitized them to senolytic treatments and apoptosis. Our results support the notion that m6A modifications critically control senescence programs, and that factors such as METTL3/METTL14 and IGF2BP1, implicated in PTCHD4 mRNA m6A metabolism, could be exploited to eliminate senescent cells for therapeutic benefit.
2024-12-18 | GSE246934 | GEO
Project description:RNA modifications, including m6A, critically modulate protein expression program in a range of cellular processes. Although cellular senescence has been linked to age-related diseases and functional declines, the landscape and impact of m6A modification are poorly understood. Here, we report a robust m6A modification of Patched-Domain Containing Protein 4 (PTCHD4) mRNA at m6A in senescent cells. The METTL3/METTL14 complex was found to mediate the m6A modification of PTCHD4 mRNA, which increased PTCHD4 mRNA stability and PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as being responsible for stabilization and increased abundance of PTCHD4 mRNA by m6A modification. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells, and sensitized them to senolytic treatments and apoptosis. Our results support the notion that m6A modifications critically control senescence programs, and that factors such as METTL3/METTL14 and IGF2BP1, implicated in PTCHD4 mRNA m6A metabolism, could be exploited to eliminate senescent cells for therapeutic benefit.
2024-12-18 | GSE247595 | GEO
Project description:RNA modifications, including m6A, critically modulate protein expression program in a range of cellular processes. Although cellular senescence has been linked to age-related diseases and functional declines, the landscape and impact of m6A modification are poorly understood. Here, we report a robust m6A modification of Patched-Domain Containing Protein 4 (PTCHD4) mRNA at m6A in senescent cells. The METTL3/METTL14 complex was found to mediate the m6A modification of PTCHD4 mRNA, which increased PTCHD4 mRNA stability and PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as being responsible for stabilization and increased abundance of PTCHD4 mRNA by m6A modification. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells, and sensitized them to senolytic treatments and apoptosis. Our results support the notion that m6A modifications critically control senescence programs, and that factors such as METTL3/METTL14 and IGF2BP1, implicated in PTCHD4 mRNA m6A metabolism, could be exploited to eliminate senescent cells for therapeutic benefit.
2024-12-18 | GSE247596 | GEO
Project description:Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival
| PRJNA1039828 | ENA
Project description:Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [CLIP-seq]
| PRJNA1039792 | ENA
Project description:Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [RNA-seq]
| PRJNA1039793 | ENA
Project description: Not available
| S-EPMC11229380 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-12-17 | GSE247621 | GEO
Project description:Cellular senescence is a key driver of age-related pathologies. This study investigates the role of the transmembrane protein PTCHD4 in cellular and organismal age-related processes. We demonstrate that PTCHD4 expression is significantly upregulated in various senescence models, including replicative and stress-induced senescence in human and mouse cells, and in multiple tissues of physiologically aged mice. Functionally, PTCHD4 deficiency attenuated the progression of cellular senescence, whereas its overexpression was shown to accelerate it. At the organismal level, PTCHD4 deficiency extended median lifespan and improved age-related declines in motor function, cognitive performance and metabolic homeostasis. In a bleomycin-induced pulmonary fibrosis model, PTCHD4 deficiency reduced lung fibrosis and preserved pulmonary function. Mechanistically, we found that PTCHD4 promotes cellular senescence by activating the AKT signaling pathway. Taken together, these findings identify PTCHD4 as a novel regulator of cellular and physiological age-related deterioration and suggest that targeting the PTCHD4-AKT axis could be an appropriate strategy for alleviating age-related functional decline.
2026-09-17 | GSE314645 | GEO
Project description:The presence of senescent cells in the aging/degenerating human disc is now well-recognized. Senescent cells are viable, cannot divide, remain metabolically active and accumulate within the disc over time. Molecular analysis of senescent cells in tissue, however, offers a special challenge since there are no cell surface markers for senescence which would let one use fluorescence-activated cell sorting as a method for separating out senescent cells. Here we use a novel experimental design using laser capture microdissection to selectively separately harvest senescent and non-senescent annulus cells in paraffin-embedded tissue, and then compare their gene expression with microarray analysis. An initial in vitro study using cultured human annulus cells was first performed to test whether there was any difference in identification of senescent cells using the accepted histochemical methodology vs. the immunofluoresent identification of cells positive for senescence-associated-ß-galactosidase in control cells and cells induced into stress-induced premature senescence via hydrogen peroxide exposure. No statistically significant difference was found between the 2 methods. Laser capture microdissection was used to separately harvest senescent and non-senescent cells from 11 human annulus specimens, and microarray analysis was used to determine gene expression levels. Genes with established relationships to senescence were found to be significantly upregulated in senescent cells vs. non-senescent cells. Additional genes related to cytokines, cell proliferation, and other cell processes were also identified. Disc Tissue samples were obtained from surgical disc procedures performed on patients with herniated discs and degenerative disc disease. Tissue was fixed and paraffin embedded. Standard laser capture microdissection (LCM) techniques were used to collect senescent cells. Remaining non-senescent cells were scraped from the histology slide. Total RNA was isolated and analyzed via mircoarray. Gene expression from senescent cells was compared to non-senescent cells. Eight histological samples were used to obtain both senescent and non-senescent cells. From an additional 3 samples, only senescent cells were harvested.
2009-07-15 | E-GEOD-17077 | biostudies-arrayexpress