Why the study?
Does the presence of an upstream open reading frame in the 5' UTR of the huntingtin gene impede its translation?
Does the presence of an upstream open reading frame in the 5' UTR of the huntingtin gene impede its translation?
The discovery of a uORF in the huntingtin gene 5' UTR reveals a novel post-transcriptional regulatory mechanism that impedes huntingtin protein synthesis, offering potential insights into Huntington's disease pathogenesis.
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.
No takes yet. Share an insight, caveat, or question.
Jong‐Min Lee (2002) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: