The physiological function of the Fe(II) and 2-oxo-glutarate dependent dioxygenase Jmjd6 in C. elegans

Jmjd6属于铁(II)和2-氧戊二酸依赖的双加氧酶家族。这些酶利用大气中的氧气来羟化它们的底物，因此能够感知氧气的张力。Jmjd6是一种赖氨酸羟化酶。它的特定底物包括核糖体蛋白和剪接因子。脊椎动物的Jmjd6基因敲除或敲除会导致严重的发育缺陷和围产期胚胎细胞死亡。Jmjd6序列在整个动物界都非常保守，然而，与脊椎动物相比，无脊椎动物模式生物中的Jmjd6基因敲除没有任何明显的发育表型。本研究的目的是研究Jmjd6在无脊椎动物中的功能。此外，我们还想找出Jmjd6是否参与线虫的低氧反应途径。我们想要分析Jmjd6功能缺失突变体的表型以及在低氧和常氧条件下Jmjd6在线虫中的表达模式。最后，我们打算用Jmjd6在线虫中进行GFP-Pull实验，以了解在无脊椎动物中，Jmjd6是否也与剪接调节器的RS结构域相互作用。作为该项目的结果，我们希望开发具有独特特性的线虫作为一种遗传上可接近的模式生物，以深入了解Jmjd6的生理功能，并从更大的角度了解酶JmjC结构域在调节细胞对氧的反应适应中的贡献。

Jmjd6 belongs to the Fe(II) and 2-oxoglutarate dependent dioxygenase family. These enzymes use atmospheric oxygen to hydroxylate their substrates and are thus capable of sensing oxygen tension. Jmjd6 is a lysine hydroxylase. Its specific substrates comprise ribosomal proteins and splice factors. Jmjd6 knockout or knockdown in vertebrates leads to severe developmental defects and perinatal embryonic cell death. The Jmjd6 sequence is very well conserved throughout the whole animal kingdom, however, in contrast to vertebrates, Jmjd6 knockdown in invertebrate model organisms does not have any obvious developmental phenotypes. The aim of this study is to study the function of Jmjd6 in invertebrates. Moreover, we want to find out, whether Jmjd6 is involved in the hypoxic response pathway in C. elegans. We want to analyse the phenotype of a Jmjd6 loss of function mutant and the expression pattern of Jmjd6 in C. elegans under hypoxic and normoxic conditions. Finally, we aim to conduct a GFP-pulldown experiment with Jmjd6 in C. elegans in order to find out whether in invertebrates Jmjd6 also interacts with RS-domains of splice modulators. As a result of this project we would like to develop C. elegans with its unique properties as a genetically approachable model organisms to obtain insight into the physiological function of Jmjd6 and at a larger perspective the contribution of enzymatic JmjC-domains to regulating adaptation of cellular responses to oxygen.