Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
Biochem J. 2013 Aug 1;453(3):357-70. doi: 10.1042/BJ20130529.
Jmjd6 (jumonji-domain-containing protein 6) is an Fe(II)- and 2OG (2-oxoglutarate)-dependent oxygenase that catalyses hydroxylation of lysine residues in proteins involved in pre-mRNA splicing. Jmjd6 plays an essential role in vertebrate embryonic development and has been shown to modulate alternative splicing in response to hypoxic stress. In the present study we show that an alternatively spliced version of Jmjd6 lacking the polyS (polyserine) domain localizes to the nucleolus, predominantly in the fibrillar centre. Jmjd6 with the polyS domain deleted also interacts with nucleolar proteins. Furthermore, co-immunoprecipitation experiments and F2H (fluorescent 2-hybrid) assays demonstrate that Jmjd6 homo-oligomerization occurs in cells. In correlation with the observed variations in the subnuclear distribution of Jmjd6, the structure of Jmjd6 oligomers in vitro changes in the absence of the polyS domain, possibly reflecting the role of the polyS domain in nuclear/nucleolar shuttling of Jmjd6.
Jmjd6（含 jumonji 结构域蛋白 6）是一种依赖 Fe(II)和 2OG（2-氧代戊二酸）的氧化酶，能够催化参与前体 mRNA 剪接的蛋白质中赖氨酸残基的羟化。Jmjd6 在脊椎动物胚胎发育中发挥着重要作用，并已被证明能够调节缺氧应激下的可变剪接。在本研究中，我们表明，一种缺乏多聚丝氨酸（polyserine）结构域的 Jmjd6 剪接变体定位于核仁，主要位于纤维中心。缺失多聚丝氨酸结构域的 Jmjd6 也与核仁蛋白相互作用。此外，共免疫沉淀实验和 F2H（荧光 2 杂交）分析表明，Jmjd6 同源寡聚体在细胞中发生。与观察到的 Jmjd6 在亚核分布中的变化相关，在没有多聚丝氨酸结构域的情况下，Jmjd6 寡聚体的结构在体外发生变化，这可能反映了多聚丝氨酸结构域在 Jmjd6 的核/核仁穿梭中的作用。
