Sudestada1, a Drosophila ribosomal prolyl-hydroxylase required for mRNA translation, cell homeostasis, and organ growth.

MAXIMILIANO J KATZ; JULIETA ACEVEDO; CHRISTOPH LEONARZ; DIEGO GALAGOVSKY; PHEBEE LIU-YI; MARCELO PÉREZ; ARMIN THALHAMMER; ROK SEKIRNIK; WEI GE; MARIANA MELANIE; MARÍA GABRIELA THOMAS; SERGIO SIMONETTA; GRACIELA LIDIA BOCCACCIO; CHRISTOPER J SCHOFIELD; MATTHEW E COCKMAN; PETER J RADCLIFFE; PABLO WAPPNER

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington DC, USA; Año: 2014 vol. 111 p. 4025 - 4030

0027-8424

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.