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http://purl.uniprot.org/citations/33674575http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33674575http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.org/dc/terms/identifier"doi:10.1038/s41467-021-21637-y"xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Hernandez J."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Subramaniam S."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Sharma M."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Michel A."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Ricci E.P."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Eshraghi M."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Blin J."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Shahani N."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Ramirez-Jarquin U.N."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Galli N."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Florescu K."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Karunadharma P.P."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/author"Urban N.T."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/name"Nat Commun"xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/pages"1461"xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/title"Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease."xsd:string
http://purl.uniprot.org/citations/33674575http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/33674575http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33674575
http://purl.uniprot.org/citations/33674575http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33674575
http://purl.uniprot.org/uniprot/#_A8K3C9-mappedCitation-33674575http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33674575
http://purl.uniprot.org/uniprot/#_D2CTD2-mappedCitation-33674575http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33674575