ArticleNucleic acids research2014
The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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112 citing papers in PubMed, 202 citations in OpenAlex.
- 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
- An ALS-associated mutation in the C-terminal α-helix of TDP-43 uncouples condensate formation and amyloid assembly.Protein science : a publication of the Protein Society · 2026Article
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- A neurotoxic cryptic peptide arising from TDP-43-dependent cryptic splicing of PKN1.Nature communications · 2026Article
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.The FEBS journal · 2026Review
- TDP-43 controls RNA structure through high affinity lattice interactions.bioRxiv : the preprint server for biology · 2025Article
- CRISPR/Cas9-MediatedAnimals : an open access journal from MDPI · 2025Article
- TDP-43 binds to RNA G-quadruplex structure and regulates mRNA stability and translation.Nucleic acids research · 2025Article
- Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.Cell · 2025Article
- Review
- Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration.Molecular neurodegeneration · 2025Review
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- Semi-synthesis of TDP-43 reveals the effects of phosphorylation in N-terminal domain on self-association.Communications chemistry · 2025Article
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- Detection of an Intermediate in the Unfolding Process of the N-Terminal Domain of TDP-43.ACS omega · 2025Article
- The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma.Cancer research · 2025Article
- scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy.PloS one · 2025Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TDP-43 is an important pathological protein that aggregates in the diseased neuronal cells and is linked to various neurodegenerative disorders. In normal cells, TDP-43 is primarily an RNA-binding protein; however, how the dimeric TDP-43 binds RNA via its two RNA recognition motifs, RRM1 and RRM2, is not clear. Here we report the crystal structure of human TDP-43 RRM1 in complex with a single-stranded DNA showing that RRM1 binds the nucleic acid extensively not only by the conserved β-sheet residues but also by the loop residues. Mutational and biochemical assays further reveal that both RRMs in TDP-43 dimers participate in binding of UG-rich RNA or TG-rich DNA with RRM1 playing a dominant role and RRM2 playing a supporting role. Moreover, RRM1 of the amyotrophic lateral sclerosis-linked mutant D169G binds DNA as efficiently as the wild type; nevertheless, it is more resistant to thermal denaturation, suggesting that the resistance to degradation is likely linked to TDP-43 proteinopathies. Taken together all the data, we suggest a model showing that the two RRMs in each protomer of TDP-43 homodimer work together in RNA binding and thus the dimeric TDP-43 recognizes long clusters of UG-rich RNA to achieve high affinity and specificity.
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