Fundación Instituto Leloir, C1405BWE Buenos Aires, Argentina.
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4025-30. doi: 10.1073/pnas.1314485111. Epub 2014 Feb 18.
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.
基因组序列预测在果蝇中存在许多依赖 2-氧戊二酸（2OG）的未知生化和生物学功能的加氧酶。核糖体蛋白羟化作用作为一种重要的 2OG 加氧酶催化途径正在出现，但它的生物学功能尚不清楚。我们报告了对果蝇核糖体加氧酶 Sudestada1（Sud1）功能的研究。与它的人类和酵母同源物 OGFOD1 和 Tpa1p 一样，我们鉴定出 Sud1 催化小核糖体亚基蛋白 RPS23 的脯氨酰羟化。与 OGFOD1 一样，Sud1 催化 RPS23 的单个脯氨酰羟化，而酵母 Tpa1p 则观察到 Pro-64 二羟化。RNAi 介导的 Sud1 敲低会阻碍不同果蝇组织的正常生长。生长受损源于细胞大小的减小和细胞数量的减少，并与翻译效率降低和内质网未折叠蛋白反应的激活相关。这伴随着 eIF2α 的磷酸化以及应激颗粒的形成，以及自噬和细胞凋亡的促进。这些观察结果，以及在配套文章中描述的酶同源物的观察结果，揭示了广泛分布的核糖体加氧酶的保守生化和生物学作用。
