ArticleeLife2021
The cooperative binding of TDP-43 to GU-rich RNA repeats antagonizes TDP-43 aggregation.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- RNA G-quadruplex-protein interactions: from nuclear RNA processing to cytoplasmic stress response and neurodegeneration.RNA biology · 2026Review
- TDP-43 controls RNA structure through high affinity lattice interactions.Nature communications · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.BMC medicine · 2026Review
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- The contribution of short tandem repeats to splicing variation in the human cortex.bioRxiv : the preprint server for biology · 2026Article
- Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD.The Journal of clinical investigation · 2026Review
- RNA G-quadruplexes mediate cooperativity in HNRNPH binding and splicing regulation.bioRxiv : the preprint server for biology · 2026Article
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- From TDP-43/RNA complex formation to disease-linked TDP-43 aggregation through a structural and cellular approach.Nature communications · 2026Article
- DNA Modulates Structural Transitions and Oligomerization Kinetics of the Functional Amyloid CRES.Journal of the American Chemical Society · 2026Article
- TDP-43 controls RNA structure through high affinity lattice interactions.bioRxiv : the preprint server for biology · 2025Article
- G4 Oligonucleotide-Based Chaperones of Heterogeneous Nuclear Ribonucleoprotein A1.International journal of molecular sciences · 2025Article
- MALAT1 regulates mRNA processing through sequence dependent RNA-RNA and RNA-protein interactions.Nucleic acids research · 2025Article
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- Epigallocatechin-3-gallate binds tandem RNA recognition motifs of TDP-43 and inhibits its aggregation.Scientific reports · 2025Article
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- SUMO2/3 conjugation of TDP-43 protects against aggregation.Science advances · 2025Article
- Detection of an Intermediate in the Unfolding Process of the N-Terminal Domain of TDP-43.ACS omega · 2025Article
- TDP-43 nuclear retention is antagonized by hypo-phosphorylation of its C-terminus in the cytoplasm.Communications biology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TDP-43 is a nuclear RNA-binding protein that forms neuronal cytoplasmic inclusions in two major neurodegenerative diseases, ALS and FTLD. While the self-assembly of TDP-43 by its structured N-terminal and intrinsically disordered C-terminal domains has been widely studied, the mechanism by which mRNA preserves TDP-43 solubility in the nucleus has not been addressed. Here, we demonstrate that tandem RNA recognition motifs of TDP-43 bind to long GU-repeats in a cooperative manner through intermolecular interactions. Moreover, using mutants whose cooperativity is impaired, we found that the cooperative binding of TDP-43 to mRNA may be critical to maintain the solubility of TDP-43 in the nucleus and the miscibility of TDP-43 in cytoplasmic stress granules. We anticipate that the knowledge of a higher order assembly of TDP-43 on mRNA may clarify its role in intron processing and provide a means of interfering with the cytoplasmic aggregation 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.