ArticleNature2014
C9orf72 nucleotide repeat structures initiate molecular cascades of disease.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 575 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
575 citing papers in PubMed, 980 citations in OpenAlex.
- RNA G-quadruplex-protein interactions: from nuclear RNA processing to cytoplasmic stress response and neurodegeneration.RNA biology · 2026Review
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
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- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026Article
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- Nuclear condensates formed by truncated mutant NEK1s impede ribosomal RNA biogenesis and drive motor dysfunction.Nature communications · 2026Article
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- RNA G-quadruplexes function as a tunable switch of FUS phase separation.Nucleic acids research · 2026Article
- VCP modulation ameliorates pathological features in C9orf72 models.Cell death & disease · 2026Article
- Phenotypic Heterogeneity in Titinopathies with Peripheral Nerve Involvement in Pediatric Age: Two Case Reports.Journal of clinical medicine · 2026Article
- RNA-binding proteins TDP-43 and FUS promote R-loop resolution and regulate transcription termination.The Journal of biological chemistry · 2026Article
- Characterizations of G-Quadruplex RNA-Protein Interactions in Living Cells.Analytical chemistry · 2026Article
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Article
- The Tale of the Guanosine Tract in Repeat Expansion Disorders.Molecular neurobiology · 2026Review
- Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.Molecular psychiatry · 2026Article
- MDS/AML-associated DDX41 helicase facilitates homologous recombination repair by potentially resolving R-loops.Nucleic acids research · 2026Article
515 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we identify a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA•DNA hybrids (R-loops). The structural polymorphism causes a repeat-length-dependent accumulation of transcripts aborted in the HRE region. These transcribed repeats bind to ribonucleoproteins in a conformation-dependent manner. Specifically, nucleolin, an essential nucleolar protein, preferentially binds the HRE G-quadruplex, and patient cells show evidence of nucleolar stress. Our results demonstrate that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provide the basis for a mechanistic model for repeat-associated neurodegenerative diseases.
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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.