title: The CPT1C 5'UTR contains a repressing upstream open reading frame that is regulated by cellular energy availability and AMPK.
abstract: BACKGROUND
  Translational control is utilized as a means of regulating gene expression in many species. In most cases, posttranscriptional regulatory mechanisms play an important role in stress response pathways and can lead to dysfunctional physiology if blocked by mutations. Carnitine Palmitoyltransferase 1 C (CPT1C), the brain-specific member of the CPT 1 family, has previously been shown to be involved in regulating metabolism in situations of energy surplus.
  
  
  RESULTS
  Sequence analysis of the CPT1C mRNA revealed that it contains an upstream open reading frame (uORF) in the 5' UTR of its mRNA. Using CPT1C 5' UTR/luciferase constructs, we investigated the role of the uORF in translational regulation. The results presented here show that translation from the CPT1C main open reading frame (mORF) is repressed by the presence of the uORF, that this repression is relieved in response to specific stress stimuli, namely glucose deprivation and palmitate-BSA treatment, and that AMPK inhibition can relieve this uORF-dependent repression.
  
  
  CONCLUSIONS
  The fact that the mORF regulation is relieved in response to a specific set of stress stimuli rather than general stress response, hints at an involvement of CPT1C in cellular energy-sensing pathways and provides further evidence for a role of CPT1C in hypothalamic regulation of energy homeostasis.
authors.affiliation: Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Ines
authors.initials: I
authors.lastname: Lohse
authors.forename: Patrick
authors.initials: P
authors.lastname: Reilly
authors.forename: Kathrin
authors.initials: K
authors.lastname: Zaugg
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*; D010168:Palmitates / Q000737:chemistry / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
chemical_list: D020121:5' Untranslated Regions; D010168:Palmitates; D011720:Pyrazoles; D011743:Pyrimidines; D012333:RNA, Messenger; C516138:dorsomorphin; D012710:Serum Albumin, Bovine; D008156:Luciferases; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases; D005947:Glucose