ArticleNucleic acids research2016
Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 112 citations in OpenAlex.
- RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD.The Journal of clinical investigation · 2026Review
- A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.PLoS biology · 2026Article
- Inhibiting Glycogen Synthase Kinase 3 Suppresses TDP-43-Mediated Neurotoxicity in a Caspase-Dependent Manner.Molecular neurobiology · 2026Article
- A partial deletion of the Tardbp 3'UTR affects TDP-43 regulation and leads to motor dysfunction in mice.Experimental animals · 2026Article
- Dominant-negative isoform of TDP-43 is regulated by ALS-linked RNA-binding proteins.The Journal of cell biology · 2025Article
- Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.Clinical and translational medicine · 2025Review
- TDP-43 Aggregate Seeding Impairs Autoregulation and Causes TDP-43 Dysfunction.bioRxiv : the preprint server for biology · 2025Article
- TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.Cell reports · 2025Article
- Alternative Splicing: Emerging Roles in Anti-Aging Strategies.Biomolecules · 2025Review
- Review
- Amyotrophic Lateral Sclerosis (ALS): An Overview of Genetic and Metabolic Signaling Mechanisms.CNS & neurological disorders drug targets · 2025Review
- TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.Frontiers in cellular neuroscience · 2025Review
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Abnormal Splicing Events due to Loss of Nuclear Function of TDP-43: Pathophysiology and Perspectives.JMA journal · 2024Review
- TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration.Cell reports · 2024Article
- Colocalization of TDP-43 and stress granules at the early stage of TDP-43 aggregation in amyotrophic lateral sclerosis.Brain pathology (Zurich, Switzerland) · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP, is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto-regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. However, it is still unclear how the autoregulatory mechanism works and how the status of autoregulation in ALS motor neurons without nuclear TDP-43 is. Here we show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons-especially neurons with mislocalized TDP-43-the amount of TARDBP mRNA is increased in the cytoplasm. Our observations indicate that nuclear TDP-43 contributes to the autoregulation and suggests that the absence of nuclear TDP-43 induces an abnormal autoregulation and increases the amount of TARDBP mRNA. The vicious cycle might accelerate the disease progression of ALS.
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