ArticleBMC biology2020
TDP-43 prevents retrotransposon activation in the Drosophila motor system through regulation of Dicer-2 activity.
Article in BMC biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Review
- Loss of TDP-43 Drives Innate Immune Activation Through Relish inInternational journal of molecular sciences · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- LINE-1 retrotransposition in a mouse TDP-43 model of neurodegeneration marks motor cortex neurons for cell-intrinsic and cell non-autonomous programmed cell death.PLoS genetics · 2025Article
- Human Endogenous Retroviruses and Diseases.MedComm · 2025Review
- Dicer Is Involved in Cytotoxicity and Motor Impairment Induced by TBPH Deficiency.Current issues in molecular biology · 2025Article
- Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.Vaccines · 2025Review
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- TDP-43-mediated amyotrophic lateral sclerosis: new/hidden insights fromFrontiers in cell and developmental biology · 2025Article
- Review
- TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk.Cell reports · 2024Article
- Invertebrate genetic models of amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- Su(var)3-9 mediates age-dependent increase in H3K9 methylation on TDP-43 promoter triggering neurodegeneration.Cell death discovery · 2023Article
- TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.International journal of molecular sciences · 2023Review
- A Novel Drosophila-based Drug Repurposing Platform Identified Fingolimod As a Potential Therapeutic for TDP-43 Proteinopathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- TDP-43 pathology inbioRxiv : the preprint server for biology · 2023Article
- Repetitive elements in aging and neurodegeneration.Trends in genetics : TIG · 2023Review
- Endogenous retroviruses and TDP-43 proteinopathy form a sustaining feedback driving intercellular spread of Drosophila neurodegeneration.Nature communications · 2023Article
- Review
- Retroviral Elements in Pathophysiology and as Therapeutic Targets for Amyotrophic Lateral Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in the small RNA-binding protein TDP-43 lead to the formation of insoluble cytoplasmic aggregates that have been associated with the onset and progression of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder affecting homeostasis of the motor system which is also characterized by aberrant expression of retrotransposable elements (RTEs). Although the TDP-43 function was shown to be required in the neurons and glia to maintain the organization of neuromuscular synapses and prevent denervation of the skeletal muscles, the molecular mechanisms involved in physiological dysregulation remain elusive. Here, we address this issue using a null mutation of the TDP-43 Drosophila homolog, TBPH.
resultsUsing genome-wide gene expression profiles, we detected a strong upregulation of RTE expression in TBPH-null Drosophila heads, while the genetic rescue of the TDP-43 function reverted these modifications. Furthermore, we found that TBPH modulates the small interfering RNA (siRNA) silencing machinery responsible for RTE repression. Molecularly, we observed that TBPH regulates the expression levels of Dicer-2 by direct protein-mRNA interactions in vivo. Accordingly, the genetic or pharmacological recovery of Dicer-2 activity was sufficient to repress retrotransposon activation and promote motoneuron axonal wrapping and synaptic growth in TBPH-null Drosophila.
conclusionsWe identified an upregulation of RTE expression in TBPH-null Drosophila heads and demonstrate that defects in the siRNA pathway lead to RTE upregulation and motoneuron degeneration. Our results describe a novel physiological role of endogenous TDP-43 in the prevention of RTE-induced neurological alterations through the modulation of Dicer-2 activity and the siRNA pathway.
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