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Inhibition of CHOP translation by a peptide encoded by an open reading frame localized in the chop 5'UTR

C Jousse1, A Bruhat, V Carraro

  • 1UR 238 - Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, 63122 Saint Genès Champanelle, France.

Nucleic Acids Research
|November 3, 2001
PubMed

Insights

The Chop gene

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • The Chop gene encodes a transcription factor crucial for cellular processes like growth, differentiation, and programmed cell death.
  • CHOP protein expression increases significantly under various cellular stresses, including endoplasmic reticulum dysfunction and DNA damage.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling CHOP protein synthesis.
  • To determine the role of the Chop transcript's 5' untranslated region (5'UTR) in regulating CHOP expression.

Main Methods:

  • Analysis of the Chop transcript's 5'UTR, including its conserved upstream open reading frame (uORF).
  • Mutational analysis of the 5' leader region and peptide coding sequences within the uORF.
  • Investigating the impact of these mutations on downstream open reading frame (ORF) expression.

Main Results:

  • The 5'UTR of the Chop transcript plays a critical role in controlling CHOP protein synthesis.
  • A conserved uORF within the 5'UTR encodes a peptide that inhibits the expression of the downstream ORF.
  • Mutational analysis indicates the uORF-encoded peptide directly inhibits downstream protein expression.

Conclusions:

  • The uORF in the Chop 5'UTR acts as a regulatory element, limiting protein synthesis.
  • This mechanism likely involves limiting ribosomal access to downstream initiation sites.
  • Understanding these regulatory mechanisms is vital due to CHOP protein's importance in cellular function.

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