ArticleNature communications2021
Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- The role of AI-assisted drug repurposing in neurological disorders: a systematic review of validation strategies, challenges and opportunities.Journal of nanobiotechnology · 2026Pooled it
- Single-cell transcriptomics and mouse model phenotyping for biomarker screen of peripheral blood in Huntington's disease.Scientific reports · 2026Article
- Ribosome Homeostasis Regulated by SETD2 Preserves Intestinal Epithelial Barrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- QuAPPro: an R shiny app for quantification and alignment of polysome profiles.BMC bioinformatics · 2026Article
- RNA Granules at the Crossroads of Synaptic Dysfunction and Neurodegeneration.Journal of neurochemistry · 2025Review
- Distinct molecular patterns in R6/2 HD mouse brain: Insights from spatiotemporal transcriptomics.Neuron · 2025Article
- Interpreting ribosome dynamics during mRNA translation.The Journal of biological chemistry · 2025Review
- Lysyl-tRNA synthetase orchestrates translation and hormone signaling during reproduction in Aedes aegypti mosquitoes.Communications biology · 2025Article
- Translation suppresses exogenous target RNA-mediated microRNA decay.Nature communications · 2025Article
- Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures.Molecular systems biology · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
- Transcriptome Study in Sicilian Patients with Huntington's Disease.Diagnostics (Basel, Switzerland) · 2025Article
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.Biology · 2025Review
- UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting.Neurology international · 2024Article
- Leveraging explainable deep learning methodologies to elucidate the biological underpinnings of Huntington's disease using single-cell RNA sequencing data.BMC genomics · 2024Article
- Two novel DnaJ chaperone proteins CG5001 and P58IPK regulate the pathogenicity of Huntington's disease related aggregates.Scientific reports · 2024Article
- Poly-GR repeats associated with ALS/FTD geneScience signaling · 2024Article
- Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Protein translation rate determines neocortical neuron fate.Nature communications · 2024Article
Corrections and comments
- Commented on by
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The polyglutamine expansion of huntingtin (mHTT) causes Huntington disease (HD) and neurodegeneration, but the mechanisms remain unclear. Here, we found that mHtt promotes ribosome stalling and suppresses protein synthesis in mouse HD striatal neuronal cells. Depletion of mHtt enhances protein synthesis and increases the speed of ribosomal translocation, while mHtt directly inhibits protein synthesis in vitro. Fmrp, a known regulator of ribosome stalling, is upregulated in HD, but its depletion has no discernible effect on protein synthesis or ribosome stalling in HD cells. We found interactions of ribosomal proteins and translating ribosomes with mHtt. High-resolution global ribosome footprint profiling (Ribo-Seq) and mRNA-Seq indicates a widespread shift in ribosome occupancy toward the 5' and 3' end and unique single-codon pauses on selected mRNA targets in HD cells, compared to controls. Thus, mHtt impedes ribosomal translocation during translation elongation, a mechanistic defect that can be exploited for HD therapeutics.
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.