Optimal translational termination requires C4 lysyl hydroxylation of eRF1

Research output: Contribution to journalArticlepeer-review

Authors

  • Tianshu Feng
  • Atsushi Yamamoto
  • Sarah e. Wilkins
  • Elizaveta Sokolova
  • Luke a. Yates
  • Martin Münzel
  • Pooja Singh
  • Richard j. Hopkinson
  • Roman Fischer
  • Matthew e. Cockman
  • Jake Shelley
  • David c. Trudgian
  • Johannes Schödel
  • James s.o. Mccullagh
  • Wei Ge
  • Benedikt m. Kessler
  • Robert j. Gilbert
  • Ludmila y. Frolova
  • Elena Alkalaeva
  • Peter j. Ratcliffe
  • Christopher j. Schofield

Colleges, School and Institutes

Abstract

Efficient stop codon recognition and peptidyl-tRNA hydrolysis are essential in order to terminate translational elongation and maintain protein sequence fidelity. Eukaryotic translational termination is mediated by a release factor complex that includes eukaryotic release factor 1 (eRF1) and eRF3. The N terminus of eRF1 contains highly conserved sequence motifs that couple stop codon recognition at the ribosomal A site to peptidyl-tRNA hydrolysis. We reveal that Jumonji domain-containing 4 (Jmjd4), a 2-oxoglutarate- and Fe(II)-dependent oxygenase, catalyzes carbon 4 (C4) lysyl hydroxylation of eRF1. This posttranslational modification takes place at an invariant lysine within the eRF1 NIKS motif and is required for optimal translational termination efficiency. These findings further highlight the role of 2-oxoglutarate/Fe(II) oxygenases in fundamental cellular processes and provide additional evidence that ensuring fidelity of protein translation is a major role of hydroxylation.

Details

Original languageEnglish
Pages (from-to)645-654
JournalMolecular Cell
Volume53
Issue number4
Early online date30 Jan 2014
Publication statusPublished - 20 Feb 2014