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

Rachelle S Singleton, 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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)4031-6
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume111
Issue number11
Early online date18 Feb 2014
DOIs
Publication statusPublished - Mar 2014

Keywords

  • 2-oxoglutarate oxygenase
  • Hypoxia
  • Ribosome
  • Translational control

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