ArticleCell reports2017
Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- A mutation in the nuclear speckle and splicing factor SRRM2 is associated with multisystem proteinopathy and causes dysregulation of synapse-associated genes.RNA (New York, N.Y.) · 2026Article
- Splicing factor Sf3b1 facilitates maintenance of neuronal dendrites by modulating mitochondrial health.Cellular and molecular life sciences : CMLS · 2025Article
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- Article
- C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Article
- Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging.Ageing research reviews · 2024Review
- The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.Cell reports · 2024Article
- Reversal ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides againstScience advances · 2023Article
- Transcriptome-wide RNA binding analysis of C9orf72 poly(PR) dipeptides.Life science alliance · 2023Article
- Alternative splicing in neurodegenerative disease and the promise of RNA therapies.Nature reviews. Neuroscience · 2023Review
- Aberrant phase separation is a common killing strategy of positively charged peptides in biology and human disease.bioRxiv : the preprint server for biology · 2023Article
- Unraveling the impact of disrupted nucleocytoplasmic transport systems inFrontiers in cellular neuroscience · 2023Review
- Article
- HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS.Acta neuropathologica · 2022Article
- Expanding Clinical Spectrum ofNeurology. Genetics · 2022Review
- Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM.Nature communications · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR) proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR) and glycine-arginine (GR) toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP) as a major interactor of PR and GR peptides. In addition, U2 snRNP, but not other splicing factors, mislocalizes from the nucleus to the cytoplasm both in C9ORF72 patient induced pluripotent stem cell (iPSC)-derived motor neurons and in HeLa cells treated with the toxic peptides. Bioinformatic studies support a specific role for U2-snRNP-dependent mis-splicing in C9ORF72 patient brains. Together, our data indicate that DPR-mediated dysfunction of U2 snRNP could account for as much as ∼44% of the mis-spliced cassette exons in C9ORF72 patient brains.
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What OpenQuestion holds
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.