ArticleNature neuroscience2025
TDP-43 loss induces cryptic polyadenylation in ALS/FTD.
Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.Nature genetics · 2026Article
- Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-frontotemporal dementia.Acta neuropathologica · 2026Article
- TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD.bioRxiv : the preprint server for biology · 2026Article
- Article
- TDP-43 controls RNA structure through high affinity lattice interactions.Nature communications · 2026Article
- Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.Journal of neurology · 2026Review
- Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice.Nature neuroscience · 2026Article
- Article
- Nanopore direct RNA sequencing and the epitranscriptome: Advances in mapping native RNA landscapes.iMeta · 2026Review
- 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
- Nuclear export modulates TDP-43 phase transition and cytoplasmic aggregation.bioRxiv : the preprint server for biology · 2026Article
- Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 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
- Lost in translation: absence of KIAA1324/ELAPOR1 protein in pathological TDP-43-affected neurons in ALS/FTD.Acta neuropathologica communications · 2026Article
- From development to disease: the neuronal role of hnRNPs through the lens ofFrontiers in cell and developmental biology · 2026Review
- TDP-43-mediated alternative polyadenylation is associated with a reduction in VPS35 and VPS29 expression in frontotemporal dementia.PLoS biology · 2026Article
- Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.bioRxiv : the preprint server for biology · 2025Article
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27 authors.
Funding
Abstract
Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 are cellular hallmarks of amyotrophic lateral sclerosis (ALS). TDP-43 nuclear loss causes de-repression of cryptic exons, yet cryptic alternative polyadenylation (APA) events have been largely overlooked. In this study, we developed a bioinformatic pipeline to reliably identify alternative last exons, 3' untranslated region (3'UTR) extensions and intronic polyadenylation APA event types, and we identified cryptic APA sites induced by TDP-43 loss in induced pluripotent stem cell (iPSC)-derived neurons. TDP-43 binding sites are enriched at sites of these cryptic events, and TDP-43 can both repress and enhance APA. All categories of cryptic APA were also identified in ALS and frontotemporal dementia (FTD) postmortem brain tissue. RNA sequencing (RNA-seq), thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) and ribosome profiling (Ribo-seq) revealed that distinct cryptic APA categories have different downstream effects on transcript levels and that cryptic 3'UTR extensions can increase RNA stability, leading to increased translation. In summary, we demonstrate that TDP-43 nuclear depletion induces cryptic APA, expanding the palette of known consequences of TDP-43.
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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.