title: OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation.
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.
authors.affiliation: Centre for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom.
authors.forename: Rachelle S
authors.initials: RS
authors.lastname: Singleton
authors.forename: Phebee
authors.initials: P
authors.lastname: Liu-Yi
authors.forename: Fabio
authors.initials: F
authors.lastname: Formenti
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.forename: Rok
authors.initials: R
authors.lastname: Sekirnik
authors.forename: Roman
authors.initials: R
authors.lastname: Fischer
authors.forename: Julie
authors.initials: J
authors.lastname: Adam
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pollard
authors.forename: Alexander
authors.initials: A
authors.lastname: Wolf
authors.forename: Armin
authors.initials: A
authors.lastname: Thalhammer
authors.forename: Christoph
authors.initials: C
authors.lastname: Loenarz
authors.forename: Emily
authors.initials: E
authors.lastname: Flashman
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Coleman
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.forename: Pablo
authors.initials: P
authors.lastname: Wappner
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Cockman
mesh_terms: D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D006900:Hydroxylation; D015151:Immunoblotting; D047468:Immunoprecipitation; D007656:Ketoglutaric Acids / Q000378:metabolism; D008156:Luciferases; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D064828:Prolyl Hydroxylases / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012269:Ribosomal Proteins / Q000378:metabolism*; D015003:Yeasts
chemical_list: D002352:Carrier Proteins; D007656:Ketoglutaric Acids; D009687:Nuclear Proteins; C548916:OGFOD1 protein, human; C484213:RPS23 protein, human; D012269:Ribosomal Proteins; D011392:Proline; D008156:Luciferases; D064828:Prolyl Hydroxylases
keywords: 2-oxoglutarate oxygenase; hypoxia; ribosome; translational control