ArticleNucleic acids research2024
Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent cell survival.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Transmembrane Protein PTCHD4 Is a Novel Regulator of Cellular Senescence and Age-Related Pathologies.Aging cell · 2026Article
- m6A-Driven Pexophagy Triggers Placental Ferroptosis to Impair Fetal Growth Upon Environmental Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An integrative single-nucleus multiomic atlas of the human left ventricle identifies gene regulatory network dynamics across cardiac development, aging, and disease.Genome biology · 2026Article
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- ORANGE: a machine learning approach for modeling tissue-specific aging from transcriptomic data.Briefings in bioinformatics · 2026Article
- Decoding the tumor-aging axis: from bench to clinical.Frontiers in immunology · 2026Review
- Deletion of METTL14, a key methylation regulator, attenuates vascular ageing.European heart journal · 2025Article
- Epigenetic regulation by WTAPP1 promotes trophoblast dysfunction in gestational diabetes via CNR1/NF-κB activation.European journal of medical research · 2025Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Plumbagin ameliorates ferroptosis of ovarian granulosa cells in polycystic ovary syndrome by down-regulating SLC7A5 m6A methylation modification through inhibition of YTHDF1.Journal of ovarian research · 2025Article
- Cellular senescence: from homeostasis to pathological implications and therapeutic strategies.Frontiers in immunology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
RNA modifications, including N6-methyladenosine (m6A), critically modulate protein expression programs in a range of cellular processes. Although the transcriptomes of cells undergoing senescence are strongly regulated, the landscape and impact of m6A modifications during senescence are poorly understood. Here, we report a robust m6A modification of PTCHD4 mRNA, encoding Patched Domain-Containing Protein 4, in senescent cells. The METTL3/METTL14 complex was found to incorporate the m6A modification on PTCHD4 mRNA; addition of m6A rendered PTCHD4 mRNA more stable and increased 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 responsible for the stabilization and increased abundance of m6A-modified PTCHD4 mRNA. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells and sensitized them to senolysis and apoptosis. Our results indicate that m6A modification of PTCHD4 mRNA increases the production of PTCHD4, a protein associated with senescent cell survival, supporting the notion that regulating m6A modification on specific mRNAs could be exploited to eliminate senescent cells for therapeutic benefit.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.