title: Loss of ncm5and mcm5wobble uridine side chains results in an altered metabolic profile.
abstract: BACKGROUND
  The Elongator complex, comprising six subunits (Elp1p-Elp6p), is required for formation of 5-carbamoylmethyl (ncm5) and 5-methoxycarbonylmethyl (mcm5) side chains on wobble uridines in 11 out of 42 tRNA species inSaccharomyces cerevisiae. Loss of these side chains reduces the efficiency of tRNA decoding during translation, resulting in pleiotropic phenotypes. Overexpression of hypomodified [Formula: see text], which in wild-type strains are modified with mcm5s2U, partially suppress phenotypes of anelp3Δstrain.
  
  
  OBJECTIVE
  To identify metabolic alterations in anelp3Δstrain and elucidate whether these metabolic alterations are suppressed by overexpression of hypomodified [Formula: see text].
  
  
  METHODS
  Metabolic profiles were obtained using untargeted GC-TOF-MS of a temperature-sensitiveelp3Δstrain carrying either an empty low-copy vector, an empty high-copy vector, a low-copy vector harboring the wild-typeELP3gene, or a high-copy vector overexpressing [Formula: see text]. The temperature sensitiveelp3Δstrain derivatives were cultivated at permissive (30 °C) or semi-permissive (34 °C) growth conditions.
  
  
  RESULTS
  Culturing anelp3Δstrain at 30 or 34 °C resulted in altered metabolism of 36 and 46 %, respectively, of all metabolites detected when compared to anelp3Δstrain carrying the wild-typeELP3gene. Overexpression of hypomodified [Formula: see text] suppressed a subset of the metabolic alterations observed in theelp3Δstrain.
  
  
  CONCLUSIONS
  Our results suggest that the presence of ncm5- and mcm5-side chains on wobble uridines in tRNA are important for metabolic homeostasis.
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Tony
authors.initials: T
authors.lastname: Karlsborn
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: A K M Firoj
authors.initials: AKMF
authors.lastname: Mahmud
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Hasan
authors.initials: H
authors.lastname: Tükenmez
authors.affiliation: Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anders S
authors.identifier: 0000-0002-0259-3503
authors.initials: AS
authors.lastname: Byström
keywords: ELP3; Elongator complex; Metabolic profiling; Metabolomics; Translation; tRNA wobble uridine modifications