2. Academic Validation
  3. Optimal translational termination requires C4 lysyl hydroxylation of eRF1

Optimal translational termination requires C4 lysyl hydroxylation of eRF1

  • Mol Cell. 2014 Feb 20;53(4):645-54. doi: 10.1016/j.molcel.2013.12.028.
Tianshu Feng 1,  Atsushi Yamamoto 1,  Sarah E Wilkins 2,  Elizaveta Sokolova 3,  Luke A Yates 4,  Martin Münzel 2,  Pooja Singh 1,  Richard J Hopkinson 2,  Roman Fischer 5,  Matthew E Cockman 1,  Jake Shelley 1,  David C Trudgian 6,  Johannes Schödel 7,  James S O McCullagh 2,  Wei Ge 2,  Benedikt M Kessler 5,  Robert J Gilbert 4,  Ludmila Y Frolova 3,  Elena Alkalaeva 3,  Peter J Ratcliffe 1,  Christopher J Schofield 2,  Mathew L Coleman 8
Affiliations

Affiliations

  • 1 Centre for Cellular and Molecular Physiology, Oxford University, Roosevelt Drive, Oxford OX3 7BN, UK.
  • 2 Chemistry Research Laboratory, Oxford University, 12 Mansfield Road, Oxford OX1 3TA, UK.
  • 3 Engelhardt Institute of Molecular Biology, the Russian Academy of Sciences, 119991 Moscow, Russia.
  • 4 Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • 5 Target Discovery Institute, Nuffield Department of Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7FZ, UK.
  • 6 Biochemistry Department and Proteomics Core, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA.
  • 7 Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen 91054, Germany.
  • 8 Centre for Cellular and Molecular Physiology, Oxford University, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: [email protected].
PMID: 24486019 DOI: 10.1016/j.molcel.2013.12.028
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.

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