ArticleScience (New York, N.Y.)2015
TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 464 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
464 citing papers in PubMed, 1 synthesis or guideline pooled it, 692 citations in OpenAlex.
- What can we learn on ALS pathophysiology from iPSC-derived motor neurons harbouring TARBDP mutations: a systematic review.Translational neurodegeneration · 2026Pooled it
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- CRYSPER and CUREIPES: two new molecular tools enabling analysis of RNA splicing and C-to-U RNA editing-inducible protein expression at single cell resolution.Nucleic acids research · 2026Article
- TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD.bioRxiv : the preprint server for biology · 2026Article
- Adenosine Deaminase-Mediated Purine Dysfunction Leads to DNA Repair Inhibition and Senescence in Sporadic Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Article
- Large-scale analysis of transcript data reveals thousands of recursive splicing events in human introns.bioRxiv : the preprint server for biology · 2026Article
- Selective vulnerability and resilience of thalamic neuronal populations in Frontotemporal Dementia.Research square · 2026Article
- ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties.bioRxiv : the preprint server for biology · 2026Article
- Article
- Article
- Review
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- A mutation in the nuclear speckle and splicing factor SRRM2 is associated with multisystem proteinopathy and causes dysregulation of synapse-associated genes.RNA (New York, N.Y.) · 2026Article
- The UNC13A cryptic exon associates with cognitive impairment in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- TDP-43 controls RNA structure through high affinity lattice interactions.Nature communications · 2026Article
- SpliceImpactR maps alternative RNA processing events driving protein functional diversity.Nucleic acids research · 2026Article
- Article
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice.Nature neuroscience · 2026Article
404 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cytoplasmic aggregation of TDP-43, accompanied by its nuclear clearance, is a key common pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, a limited understanding of this RNA-binding protein (RBP) impedes the clarification of pathogenic mechanisms underlying TDP-43 proteinopathy. In contrast to RBPs that regulate splicing of conserved exons, we found that TDP-43 repressed the splicing of nonconserved cryptic exons, maintaining intron integrity. When TDP-43 was depleted from mouse embryonic stem cells, these cryptic exons were spliced into messenger RNAs, often disrupting their translation and promoting nonsense-mediated decay. Moreover, enforced repression of cryptic exons prevented cell death in TDP-43-deficient cells. Furthermore, repression of cryptic exons was impaired in ALS-FTD cases, suggesting that this splicing defect could potentially underlie TDP-43 proteinopathy.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.