Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Genome sequences predict the presence of many 2-oxoglutarate (2OG)-dependent oxygenases of unknown biochemical and biological functions in Drosophila. Ribosomal protein hydroxylation is emerging as an important 2OG oxygenase catalyzed pathway, but its biological functions are unclear. We report investigations on the function of Sudestada1 (Sud1), a Drosophila ribosomal oxygenase. As with its human and yeast homologs, OGFOD1 and Tpa1p, respectively, we identified Sud1 to catalyze prolyl-hydroxylation of the small ribosomal subunit protein RPS23. Like OGFOD1, Sud1 catalyzes a single prolyl-hydroxylation of RPS23 in contrast to yeast Tpa1p, where Pro-64 dihydroxylation is observed. RNAi-mediated Sud1 knockdown hinders normal growth in different Drosophila tissues. Growth impairment originates from both reduction of cell size and diminution of the number of cells and correlates with impaired translation efficiency and activation of the unfolded protein response in the endoplasmic reticulum. This is accompanied by phosphorylation of eIF2α and concomitant formation of stress granules, as well as promotion of autophagy and apoptosis. These observations, together with those on enzyme homologs described in the companion articles, reveal conserved biochemical and biological roles for a widely distributed ribosomal oxygenase.

Original publication

DOI

10.1073/pnas.1314485111

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

18/03/2014

Volume

111

Pages

4025 - 4030

Keywords

dioxygenase, fruit fly, proline, ribosome, tranlational stress, Animals, Animals, Genetically Modified, Apoptosis, Autophagy, Blotting, Western, Body Weights and Measures, Chromatography, Liquid, DNA Primers, Drosophila, Drosophila Proteins, Fat Body, Female, Gene Knockdown Techniques, Homeostasis, Hydroxylation, Prolyl Hydroxylases, Protein Biosynthesis, Protein Processing, Post-Translational, RNA Interference, Real-Time Polymerase Chain Reaction, Ribosomal Proteins, Tandem Mass Spectrometry, Unfolded Protein Response