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Nucleic Acids Res
2002 Dec 01;3023:5110-9. doi: 10.1093/nar/gkf664.
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An upstream open reading frame impedes translation of the huntingtin gene.
Lee J
,
Park EH
,
Couture G
,
Harvey I
,
Garneau P
,
Pelletier J
.
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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.
Coles,
Analysis of the 5' upstream sequence of the Huntington's disease (HD) gene shows six new rare alleles which are unrelated to the age at onset of HD.
1997, Pubmed
Coles,
Analysis of the 5' upstream sequence of the Huntington's disease (HD) gene shows six new rare alleles which are unrelated to the age at onset of HD.
1997,
Pubmed
Coles,
Functional analysis of the Huntington's disease (HD) gene promoter.
1998,
Pubmed
Davies,
Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation.
1997,
Pubmed
DiFiglia,
Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.
1997,
Pubmed
Duyao,
Inactivation of the mouse Huntington's disease gene homolog Hdh.
1995,
Pubmed
Fang,
Evolutionarily conserved features of the arginine attenuator peptide provide the necessary requirements for its function in translational regulation.
2000,
Pubmed
Ferrante,
Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum.
1997,
Pubmed
Gaba,
Physical evidence for distinct mechanisms of translational control by upstream open reading frames.
2001,
Pubmed
Gardiner-Garden,
CpG islands in vertebrate genomes.
1987,
Pubmed
Gutekunst,
Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies.
1995,
Pubmed
Harvey,
Forced engagement of a RNA/protein complex by a chemical inducer of dimerization to modulate gene expression.
2002,
Pubmed
Hemmings-Mieszczak,
Termination and peptide release at the upstream open reading frame are required for downstream translation on synthetic shunt-competent mRNA leaders.
2000,
Pubmed
Hinnebusch,
Translational regulation of yeast GCN4. A window on factors that control initiator-trna binding to the ribosome.
1997,
Pubmed
Holzmann,
Functional characterization of the human Huntington's disease gene promoter.
2001,
Pubmed
Holzmann,
Isolation and characterization of the rat huntingtin promoter.
1998,
Pubmed
Jou,
Evidence from antibody studies that the CAG repeat in the Huntington disease gene is expressed in the protein.
1995,
Pubmed
Kozak,
Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes.
1981,
Pubmed
Kozak,
An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
1987,
Pubmed
Kozak,
Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes.
1987,
Pubmed
Lin,
Structural analysis of the 5' region of mouse and human Huntington disease genes reveals conservation of putative promoter region and di- and trinucleotide polymorphisms.
1995,
Pubmed
Lovett,
Ribosome regulation by the nascent peptide.
1996,
Pubmed
Mangiarini,
Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.
1996,
Pubmed
Marth,
Translational activation of the lck proto-oncogene.
1988,
Pubmed
McCarthy,
Posttranscriptional control of gene expression in yeast.
1998,
Pubmed
Morris,
Upstream open reading frames as regulators of mRNA translation.
2000,
Pubmed
NULL,
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
1993,
Pubmed
Nasir,
Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes.
1995,
Pubmed
Nasir,
Huntington disease: new insights into the relationship between CAG expansion and disease.
1996,
Pubmed
Novelletto,
Polymorphism analysis of the huntingtin gene in Italian families affected with Huntington disease.
1994,
Pubmed
Pause,
Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.
1994,
Pubmed
Pelletier,
Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency.
1985,
Pubmed
Pelletier,
Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA.
1988,
Pubmed
Rechavi,
Activation of a cellular oncogene by DNA rearrangement: possible involvement of an IS-like element.
1982,
Pubmed
Rubinsztein,
Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.
1996,
Pubmed
Schmitt,
Expression of the Huntington disease gene in rodents: cloning the rat homologue and evidence for downregulation in non-neuronal tissues during development.
1995,
Pubmed
Steel,
Elements in the murine c-mos messenger RNA 5'-untranslated region repress translation of downstream coding sequences.
1996,
Pubmed
Strong,
Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues.
1993,
Pubmed
Svitkin,
Complete translation of encephalomyocarditis virus RNA and faithful cleavage of virus-specific proteins in a cell-free system from Krebs-2 cells.
1978,
Pubmed
Trottier,
Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form.
1995,
Pubmed
Wang,
Arginine-specific regulation mediated by the Neurospora crassa arg-2 upstream open reading frame in a homologous, cell-free in vitro translation system.
1997,
Pubmed
Zeitlin,
Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue.
1995,
Pubmed
