Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants

PLoS Genet. 2009 Jul;5(7):e1000561. doi: 10.1371/journal.pgen.1000561. Epub 2009 Jul 10.


Elongator is a six subunit protein complex, conserved from yeast to humans. Mutations in the human Elongator homologue, hELP1, are associated with the neurological disease familial dysautonomia. However, how Elongator functions in metazoans, and how the human mutations affect neural functions is incompletely understood. Here we show that in Caenorhabditis elegans, ELPC-1 and ELPC-3, components of the Elongator complex, are required for the formation of the 5-carbamoylmethyl and 5-methylcarboxymethyl side chains of wobble uridines in tRNA. The lack of these modifications leads to defects in translation in C. elegans. ELPC-1::GFP and ELPC-3::GFP reporters are strongly expressed in a subset of chemosensory neurons required for salt chemotaxis learning. elpc-1 or elpc-3 gene inactivation causes a defect in this process, associated with a posttranscriptional reduction of neuropeptide and a decreased accumulation of acetylcholine in the synaptic cleft. elpc-1 and elpc-3 mutations are synthetic lethal together with those in tuc-1, which is required for thiolation of tRNAs having the 5'methylcarboxymethyl side chain. elpc-1; tuc-1 and elpc-3; tuc-1 double mutants display developmental defects. Our results suggest that, by its effect on tRNA modification, Elongator promotes both neural function and development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Chemotaxis
  • Cholinesterase Inhibitors
  • Fertility
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Life Cycle Stages
  • Microscopy, Fluorescence
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nucleic Acid Conformation
  • Protein Biosynthesis
  • RNA, Transfer / metabolism*
  • Temperature
  • Tubulin / metabolism
  • Uridine / analogs & derivatives
  • Uridine / metabolism


  • Caenorhabditis elegans Proteins
  • Cholinesterase Inhibitors
  • Nerve Tissue Proteins
  • Tubulin
  • Green Fluorescent Proteins
  • 5-methoxycarbonylmethyluridine
  • 5-carbamoylmethyluridine
  • RNA, Transfer
  • Uridine