OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation

  • Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4031-6. doi: 10.1073/pnas.1314482111.
Rachelle S Singleton  1 ,  Phebee Liu-Yi ,  Fabio Formenti ,  Wei Ge ,  Rok Sekirnik ,  Roman Fischer ,  Julie Adam ,  Patrick J Pollard ,  Alexander Wolf ,  Armin Thalhammer ,  Christoph Loenarz ,  Emily Flashman ,  Atsushi Yamamoto ,  Mathew L Coleman ,  Benedikt M Kessler ,  Pablo Wappner ,  Christopher J Schofield ,  Peter J Ratcliffe ,  Matthew E Cockman
Affiliations
  • 1. Centre for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom.
PMID: 24550447 DOI: 10.1073/pnas.1314482111
Abstract

2-Oxoglutarate (2OG) and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1) is predicted to be a conserved 2OG oxygenase, the catalytic domain of which is related to hypoxia-inducible factor prolyl hydroxylases. OGFOD1 homologs in yeast are implicated in diverse cellular functions ranging from oxygen-dependent regulation of sterol response genes (Ofd1, Schizosaccharomyces pombe) to translation termination/mRNA polyadenylation (Tpa1p, Saccharomyces cerevisiae). However, neither the biochemical activity of OGFOD1 nor the identity of its substrate has been defined. Here we show that OGFOD1 is a prolyl hydroxylase that catalyzes the posttranslational hydroxylation of a highly conserved residue (Pro-62) in the small ribosomal protein S23 (RPS23). Unusually OGFOD1 retained a high affinity for, and forms a stable complex with, the hydroxylated RPS23 substrate. Knockdown or inactivation of OGFOD1 caused a cell type-dependent induction of stress granules, translational arrest, and growth impairment in a manner complemented by wild-type but not inactive OGFOD1. The work identifies a human prolyl hydroxylase with a role in translational regulation.

Keywords
2-oxoglutarate oxygenase; hypoxia; ribosome; translational control.