ArticleNucleic acids research2005
Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene.
Article in Nucleic acids research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 114 papers.
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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.
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Who cites it
114 citing papers in PubMed, 221 citations in OpenAlex.
- Therapeutic targeting of the conserved region within the low-complexity domain of TDP-43 is neuroprotective and extends survival in amyotrophic lateral sclerosis mice.Nature aging · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.PLoS biology · 2026Article
- Plasma TAR DNA-binding protein 43 (TDP-43) levels in a population-based cohort of older adults: The cardiovascular health study.Journal of Alzheimer's disease : JAD · 2025Article
- Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.The Lancet. Neurology · 2025Review
- Membrane Charge Drives the Aggregation of TDP-43 Pathological Fragments.Journal of the American Chemical Society · 2025Article
- Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan.Journal of neuropathology and experimental neurology · 2025Article
- TDP-43 Aggregate Seeding Impairs Autoregulation and Causes TDP-43 Dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Implications of TDP-43 in non-neuronal systems.Cell communication and signaling : CCS · 2023Review
- Altered TDP-43 Structure and Function: Key Insights into Aberrant RNA, Mitochondrial, and Cellular and Systemic Metabolism in Amyotrophic Lateral Sclerosis.Metabolites · 2022Review
- Regulation of Neurodegeneration-associated Protein Fragments by the N-degron Pathways.Neurotoxicity research · 2022Review
- Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey.Biomedicines · 2022Review
- HnRNP K mislocalisation is a novel protein pathology of frontotemporal lobar degeneration and ageing and leads to cryptic splicing.Acta neuropathologica · 2021Article
- TDP-43 and Inflammation: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.International journal of molecular sciences · 2021Review
- Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies.Biomedicines · 2021Review
- Triad of TDP43 control in neurodegeneration: autoregulation, localization and aggregation.Nature reviews. Neuroscience · 2021Review
- TDP-43 dysfunction results in R-loop accumulation and DNA replication defects.Journal of cell science · 2020Article
- The role of TDP-43 propagation in neurodegenerative diseases: integrating insights from clinical and experimental studies.Experimental & molecular medicine · 2020Review
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
- TDP-43: From Alzheimer's Disease to Limbic-Predominant Age-Related TDP-43 Encephalopathy.Frontiers in molecular neuroscience · 2020Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern · 2023-02-11Concerns/Issues about Data · Duplication of/in Image ·
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- Erratum issued
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Exon 3 of the human apolipoprotein A-II (apoA-II) gene is efficiently included in the mRNA although its acceptor site is significantly weak because of a peculiar (GU)16 tract instead of a canonical polypyrimidine tract within the intron 2/exon 3 junction. Our previous studies demonstrated that the SR proteins ASF/SF2 and SC35 bind specifically an exonic splicing enhancer (ESE) within exon 3 and promote exon 3 splicing. In the present study, we show that the ESE is necessary only in the proper context. In addition, we have characterized two novel sequences in the flanking introns that modulate apoA-II exon 3 splicing. There is a G-rich element in intron 2 that interacts with hnRNPH1 and inhibits exon 3 splicing. The second is a purine rich region in intron 3 that binds SRp40 and SRp55 and promotes exon 3 inclusion in mRNA. We have also found that the (GU) repeats in the apoA-II context bind the splicing factor TDP-43 and interfere with exon 3 definition. Significantly, blocking of TDP-43 expression by small interfering RNA overrides the need for all the other cis-acting elements making exon 3 inclusion constitutive even in the presence of disrupted exonic and intronic enhancers. Altogether, our results suggest that exonic and intronic enhancers have evolved to balance the negative effects of the two silencers located in intron 2 and hence rescue the constitutive exon 3 inclusion in apoA-II mRNA.
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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.