The atypical protein kinase RIOK-2 is a non-ribosomal factor essential for ribosome maturation in yeast and human cells; however, little is known about its physiological role in pathogens. Our earlier work examined the expression profile of a RIOK-2 gene (Ss-riok-2) in Strongyloides stercoralis – a prevalent nematode parasite of dogs and humans. Herein, we demonstrate that Ss-RIOK-2 encodes a catalytically active kinase, distributed primarily in the cytoplasm of intestinal and hypodermal cells in transgenic larvae. Its expression oscillates as the free-living L1s develop into infective L3s. Overexpression of a catalytically impaired Ss-RIOK-2-D228A mutant delayed the development of transgenic larvae, while ectopic expression of another dominant negative isoform with a mutation in the ATP-binding site (K123A) abrogated the process of egg hatching, which could be rescued by co-expressing a wild-type Ss-RIOK-2 but not by its Ss-RIOK-1 ortholog. Collectively, our findings show a critical and specific role of Ss-RIOK-2 during the development of a pathogenic roundworm, which can be exploited to develop anti-infectives.

非典型蛋白激酶 RIOK-2 是一种非核糖体因子，对酵母和人类细胞中的核糖体成熟至关重要；然而，人们对其在病原体中的生理作用知之甚少。我们早期的工作检查了粪类圆线虫中RIOK-2 基因 ( Ss-riok-2 )的表达谱- 一种犬和人类普遍存在的线虫寄生虫。在本文中，我们表明，SS- RIOK-2编码具有催化活性的激酶，主要在肠和皮下细胞在转基因幼虫细胞质分布。它的表达随着自由生活的 L1s 发展成具有感染性的 L3s 而波动。过度表达催化受损的Ss-RIOK-2-D228A 突变体延迟了转基因幼虫的发育，而另一种在 ATP 结合位点 (K123A) 突变的显性负同种型的异位表达取消了卵孵化过程，这可以通过共同表达野生-type Ss- RIOK-2 但不是通过其Ss- RIOK-1 直系同源物。总的来说，我们的研究结果显示的关键和具体作用SS-致病性蛔虫，它可以用来开发抗感染药物的开发过程中RIOK-2。