ArticleRNA biology2013
Aberrantly spliced HTT, a new player in Huntington's disease pathogenesis.
Article in RNA biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Pooled it
- Forces that shape the transcriptome: Linking cellular mechanosensing to mRNA splicing.The Journal of biological chemistry · 2026Review
- A distal promoter and aberrant splicing enable canonical translation of out-of-frame proteins in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- Revolutionizing Huntington's Disease Treatment: Breakthroughs in AAV-Mediated Gene Therapy.Cells · 2025Review
- Distinct molecular patterns in R6/2 HD mouse brain: Insights from spatiotemporal transcriptomics.Neuron · 2025Article
- Genetic modifiers of somatic expansion and clinical phenotypes in Huntington's disease highlight shared and tissue-specific effects.Nature genetics · 2025Article
- mEMBO reports · 2024Article
- Huntingtin HTT1a is generated in a CAG repeat-length-dependent manner in human tissues.Molecular medicine (Cambridge, Mass.) · 2024Article
- CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.Molecular cell · 2024Article
- Article
- CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.bioRxiv : the preprint server for biology · 2023Article
- IKBKB reduces huntingtin aggregation by phosphorylating serine 13 via a non-canonical IKK pathway.Life science alliance · 2023Article
- Native functions of short tandem repeats.eLife · 2023Article
- Neuroprotectant Effects of Hibiscetin in 3-Nitropropionic Acid-Induced Huntington's Disease via Subsiding Oxidative Stress and Modulating Monoamine Neurotransmitters in Rats Brain.Molecules (Basel, Switzerland) · 2023Article
- Article
- Kynurenine 3-Monooxygenase Interacts with Huntingtin at the Outer Mitochondrial Membrane.Biomedicines · 2022Article
- Article
- Huntington's disease: nearly four decades of human molecular genetics.Human molecular genetics · 2021Review
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- Ellagic acid prevents 3-nitropropionic acid induced symptoms of Huntington's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Huntington's disease (HD) is an adult-onset neurodegenerative disorder caused by a mutated CAG repeat in the huntingtin gene that is translated into an expanded polyglutamine tract. The clinical manifestation of HD is a progressive physical, cognitive, and psychiatric deterioration that is eventually fatal. The mutant huntingtin protein is processed into several smaller fragments, which have been implicated as critical factors in HD pathogenesis. The search for proteases responsible for their production has led to the identification of several cleavage sites on the huntingtin protein. However, the origin of the small N-terminal fragments that are found in HD postmortem brains has remained elusive. Recent mapping of huntingtin fragments in a mouse model demonstrated that the smallest N-terminal fragment is an exon 1 protein. This discovery spurred our hypothesis that mis-splicing as opposed to proteolysis could be generating the smallest huntingtin fragment. We demonstrated that mis-splicing of mutant huntingtin intron 1 does indeed occur and results in a short polyadenylated mRNA, which is translated into an exon 1 protein. The exon 1 protein fragment is highly pathogenic. Transgenic mouse models containing just human huntingtin exon 1 develop a rapid onset of HD-like symptoms. Our finding that a small, mis-spliced HTT transcript and corresponding exon 1 protein are produced in the context of an expanded CAG repeat has unraveled a new molecular mechanism in HD pathogenesis. Here we present detailed models of how mis-splicing could be facilitated, what challenges remain in this model, and implications for therapeutic studies.
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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.