ArticleActa neuropathologica2018
Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated ALS/FTD.
Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
49 citing papers in PubMed, 67 citations in OpenAlex.
- The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.Biomolecules · 2026Review
- Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Article
- From development to disease: the neuronal role of hnRNPs through the lens ofFrontiers in cell and developmental biology · 2026Review
- Exploring the versatility ofFly · 2025Review
- High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation.Nucleic acids research · 2025Article
- Neuronal polyunsaturated fatty acids are protective in ALS/FTD.Nature neuroscience · 2025Article
- The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.Cell reports · 2024Article
- PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature in C9orf72 ALS/FTD neurons.Nature neuroscience · 2024Article
- Invertebrate genetic models of amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- GActa neuropathologica · 2023Article
- A monocarboxylate transporter rescues frontotemporal dementia and Alzheimer's disease models.PLoS genetics · 2023Article
- Toxicity ofLife science alliance · 2023Article
- Article
- Repeat-associated non-AUG translation induces cytoplasmic aggregation of CAG repeat-containing RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Development of a sensitive trial-ready poly(GP) CSF biomarker assay forJournal of neurology, neurosurgery, and psychiatry · 2022Article
- Biomarkers in Human Peripheral Blood Mononuclear Cells: The State of the Art in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
- Frontotemporal Dementia and Glucose Metabolism.Frontiers in neuroscience · 2022Review
- RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Neurodegeneration may occur via transcription of the repeats into inherently toxic repetitive sense and antisense RNA species, or via repeat-associated non-ATG initiated translation (RANT) of sense and antisense RNA into toxic dipeptide repeat proteins. We have previously demonstrated that regular interspersion of repeat RNA with stop codons prevents RANT (RNA-only models), allowing us to study the role of repeat RNA in isolation. Here we have created novel RNA-only Drosophila models, including the first models of antisense repeat toxicity, and flies expressing extremely large repeats, within the range observed in patients. We generated flies expressing ~ 100 repeat sense or antisense RNA either as part of a processed polyadenylated transcript or intronic sequence. We additionally created Drosophila expressing > 1000 RNA-only repeats in the sense direction. When expressed in adult Drosophila neurons polyadenylated repeat RNA is largely cytoplasmic in localisation, whilst intronic repeat RNA forms intranuclear RNA foci, as does > 1000 repeat RNA, thus allowing us to investigate both nuclear and cytoplasmic RNA toxicity. We confirmed that these RNA foci are capable of sequestering endogenous Drosophila RNA-binding proteins, and that the production of dipeptide proteins (poly-glycine-proline, and poly-glycine-arginine) is suppressed in our models. We find that neither cytoplasmic nor nuclear sense or antisense RNA are toxic when expressed in adult Drosophila neurons, suggesting they have a limited role in disease pathogenesis.
Indexed as
Identifiers
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.