一个上游开放阅读框阻碍亨廷顿基因的翻译。
An upstream open reading frame impedes translation of the huntingtin gene.
作者信息
Lee Joseph, Park Eun Hee, Couture Graeme, Harvey Isabelle, Garneau Philippe, Pelletier Jerry
机构信息
Department of Biochemistry and McGill Cancer Center, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec H3G 1Y6, Canada.
出版信息
Nucleic Acids Res. 2002 Dec 1;30(23):5110-9. doi: 10.1093/nar/gkf664.
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.
摘要
亨廷顿基因内CAG序列的扩增会导致产生一种具有延伸的聚谷氨酰胺序列的蛋白质，这是引发亨廷顿舞蹈症的原因。我们在此表明，亨廷顿基因的5'非翻译区（UTR）在控制亨廷顿蛋白的合成中起着重要作用。特别是，5'UTR包含一个编码21个氨基酸肽的上游开放阅读框（uORF）。我们证明，这个uORF的存在会对亨廷顿mRNA的表达产生负面影响。我们的结果表明，uORF在限制核糖体进入下游起始位点方面发挥作用。涉及亨廷顿蛋白转录后调控的机制尚未完全了解，这可能是调节亨廷顿蛋白水平的一种重要方式。
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