title: An upstream open reading frame impedes translation of the huntingtin gene.
abstract: Expansion of a CAG tract within the huntingtin gene, leading to the production of a protein with an expanded polyglutamine tract, is responsible for Huntington's disease. We show here that the 5' untranslated region (UTR) of the huntingtin gene plays an important role in controlling the synthesis of huntingtin. In particular, the 5' UTR contains an upstream open reading frame (uORF) encoding a 21 amino acid peptide. We demonstrate that the presence of this uORF negatively influences expression from the huntingtin mRNA. Our results suggest a role for the uORF in limiting ribosomal access to downstream initiation sites. Mechanisms involving the post-transcriptional regulation of huntingtin are not well understood, and this may be an important way of regulating huntingtin protein levels.
authors.affiliation: Department of Biochemistry and McGill Cancer Center, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lee
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Park
authors.forename: Graeme
authors.initials: G
authors.lastname: Couture
authors.forename: Isabelle
authors.initials: I
authors.lastname: Harvey
authors.forename: Philippe
authors.initials: P
authors.lastname: Garneau
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D000071058:Huntingtin Protein; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism; D024363:Transcription Initiation Site; D014981:Xenopus
chemical_list: D020121:5' Untranslated Regions; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins