ArticleThe Journal of clinical investigation2025
TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in amyotrophic lateral sclerosis and frontotemporal dementia.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.Nature genetics · 2026Article
- TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD.bioRxiv : the preprint server for biology · 2026Article
- Article
- The retroelement-derived human protein PEG10 is a regulator of mRNA splicing in neurons.bioRxiv : the preprint server for biology · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026Review
- Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex.Nature communications · 2026Article
- Article
- Lost in translation: absence of KIAA1324/ELAPOR1 protein in pathological TDP-43-affected neurons in ALS/FTD.Acta neuropathologica communications · 2026Article
- Human iPSC-derived motor neurons as a platform for elucidating TDP-43-related amyotrophic lateral sclerosis pathogenesis: a mini review.Frontiers in molecular neuroscience · 2026Review
- TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.PLoS biology · 2026Article
- RNA polyadenylation altered by TDP43 loss of function.Nature reviews. Neurology · 2026Article
- The Dual Role of Exosome-Mediated Central-Peripheral Immune Dialogue in Amyotrophic Lateral Sclerosis-Associated Neuroinflammation.Journal of inflammation research · 2026Review
- Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.bioRxiv : the preprint server for biology · 2025Article
- Sensitivity to TDP-43 loss and degradation resistance determine cryptic exon biomarker potential.bioRxiv : the preprint server for biology · 2025Article
- TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.Nature neuroscience · 2025Article
- TDP-43 loss induces cryptic polyadenylation in ALS/FTD.Nature neuroscience · 2025Article
- TDP-43 loss brings RNA to a twist ending.Nature neuroscience · 2025Article
- Nonsense-mediated decay masks cryptic splicing events caused by TDP-43 loss.bioRxiv : the preprint server for biology · 2025Article
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Abstract
Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from an RNA-Seq (DaPars) tool to ALS/FTD transcriptome datasets and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei. Importantly, many identified APA genes highlight pathways implicated in ALS/FTD pathogenesis. To determine the functional relevance of APA elicited by TDP-43 nuclear depletion, we examined microtubule affinity regulating kinase 3 (MARK3). Nuclear loss of TDP-43 yielded increased expression of MARK3 transcripts with longer 3' UTRs, corresponding with a change in the subcellular distribution of MARK3 and increased neuronal tau S262 phosphorylation. Our findings define changes in polyadenylation site selection as a previously understudied feature of TDP-43-driven disease pathology in ALS/FTD and highlight a potentially important mechanistic link between TDP-43 dysfunction and tau regulation.
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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 Socratic graph.