ArticleActa neuropathologica2023
RNA methyltransferase NSun2 deficiency promotes neurodegeneration through epitranscriptomic regulation of tau phosphorylation.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Integrating cell-type-specific gene expression and genome-wide associations identifies risk genes for schizophrenia.Molecular psychiatry · 2026Pooled it
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- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Neuromodulatory role and therapeutic potential of N 6 -methyladenosine RNA methylation in neurodegenerative diseases.Neural regeneration research · 2026Article
- Role of Folate Metabolism in Neurodegenerative Diseases: Insight from Experimental and Clinical Studies.Current nutrition reports · 2026Review
- Spinal Cord Stimulation Alleviates Spinal Cord Injury-Induced Neuropathic Pain Via mNeurochemical research · 2026Article
- AI-driven virtual screening platform identifies novel NSUN2 inhibitor candidates for targeted cancer therapy: a computational drug discovery approach.NPJ precision oncology · 2026Article
- Generation of hiPSC-Derived Brain Microvascular Endothelial Cells Using Directed Differentiation and Transcriptional Reprogramming.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- NSUN2-Mediated mInternational journal of general medicine · 2026Review
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- MicroRNA chemical modifications in post-transcriptional gene silencing and human diseases.Molecular therapy. Nucleic acids · 2025Review
- Review
- Targeting tRNA methyltransferases: from molecular mechanisms to drug discovery.Science China. Life sciences · 2025Review
- Epitranscriptomic alterations induced by environmental toxins: implications for RNA modifications and disease.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Review
- N6-methyladenosine (m6A) dysregulation contributes to network excitability in temporal lobe epilepsy.JCI insight · 2025Article
- Article
- Neuron-Specific Glycine Metabolism Links Transfer RNA Epitranscriptomic Regulation to Complex Behaviors.Biological psychiatry global open science · 2025Article
- NSUN2-Mediated RNA 5-Methylcytosine Modification of PTEN Regulates Cognitive Impairments of Mice with Sleep Deprivation and Autophagy Through PI3K/AKT Signaling.Neuromolecular medicine · 2025Article
- Methylations in dilated cardiomyopathy and heart failure.Frontiers in cardiovascular medicine · 2025Review
- RNA m5C modification: from physiology to pathology and its biological significance.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Epitranscriptomic regulation adds a layer of post-transcriptional control to brain function during development and adulthood. The identification of RNA-modifying enzymes has opened the possibility of investigating the role epitranscriptomic changes play in the disease process. NOP2/Sun RNA methyltransferase 2 (NSun2) is one of the few known brain-enriched methyltransferases able to methylate mammalian non-coding RNAs. NSun2 loss of function due to autosomal-recessive mutations has been associated with neurological abnormalities in humans. Here, we show NSun2 is expressed in adult human neurons in the hippocampal formation and prefrontal cortex. Strikingly, we unravel decreased NSun2 protein expression and an increased ratio of pTau/NSun2 in the brains of patients with Alzheimer's disease (AD) as demonstrated by Western blotting and immunostaining, respectively. In a well-established Drosophila melanogaster model of tau-induced toxicity, reduction of NSun2 exacerbated tau toxicity, while overexpression of NSun2 partially abrogated the toxic effects. Conditional ablation of NSun2 in the mouse brain promoted a decrease in the miR-125b m6A levels and tau hyperphosphorylation. Utilizing human induced pluripotent stem cell (iPSC)-derived neuronal cultures, we confirmed NSun2 deficiency results in tau hyperphosphorylation. We also found that neuronal NSun2 levels decrease in response to amyloid-beta oligomers (AβO). Notably, AβO-induced tau phosphorylation and cell toxicity in human neurons could be rescued by overexpression of NSun2. Altogether, these results indicate that neuronal NSun2 deficiency promotes dysregulation of miR-125b and tau phosphorylation in AD and highlights a novel avenue for therapeutic targeting.
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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 OpenQuestion graph.