Histone arginine demethylase JMJD6 is linked to stress granule assembly through demethylation of the stress granule–nucleating protein G3BP1
Histone arginine demethylase JMJD6 is linked to stress granule assembly through demethylation of the stress granule–nucleating protein G3BP1
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DOI：
10.1074/jbc.m117.800706
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
W. Tsai;Lucas C. Reineke;Antrix Jain;S. Jung;R. Lloyd
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文献类型：
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作者：
W. Tsai;Lucas C. Reineke;Antrix Jain;S. Jung;R. Lloyd
应激颗粒（SG）是一种无膜细胞器，是停滞的翻译起始复合物和mRNA的缩合物。SG形成是对环境应激的细胞保护反应，并且是由涉及低氨基酸复杂性区域和SG组分的不明确的翻译后修饰的蛋白质相互作用引起的。许多RNA结合蛋白是甲基化的，我们以前证明了有效的SG成核蛋白G3BP1是由蛋白质精氨酸甲基转移酶1和5（PRMT1和PRMT5）甲基化。G3BP1甲基化抑制SG形成并且是可逆的。在这里，我们在功能上将JMJD6（Jumonji C结构域包含蛋白6）与G3BP1去甲基化联系起来。我们的研究结果表明，JMJD6是一种新的SG组件，与G3BP1复合物相互作用，其表达减少G3BP1单甲基化和不对称二甲基化在三个精氨酸残基。JMJD6的敲低抑制了SG形成和G3BP1去甲基化，但SG形成和G3BP1去甲基化被具有催化活性但不是突变体JMJD6拯救。这些结果表明，JMJD6直接或间接地作为G3BP1的精氨酸脱甲基酶发挥作用，促进SG形成。
Stress granules (SG) are membrane-less organelles that are condensates of stalled translation initiation complexes and mRNAs. SG formation is a cytoprotective response to environmental stress and results from protein interactions involving regions of low amino acid complexity and poorly defined post-translational modifications of SG components. Many RNA-binding proteins are methylated, and we previously demonstrated that the potent SG–nucleating protein G3BP1 is methylated by protein arginine methyltransferase 1 and 5 (PRMT1 and PRMT5). G3BP1 methylation represses SG formation and is reversible. Here we functionally link JMJD6 (Jumonji C domain-containing protein 6) to G3BP1 demethylation. Our findings reveal that JMJD6 is a novel SG component that interacts with G3BP1 complexes, and its expression reduces G3BP1 monomethylation and asymmetric dimethylation at three Arg residues. Knockdown of JMJD6 repressed SG formation and G3BP1 demethylation, but SG formation and G3BP1 demethylation were rescued with catalytically active but not mutant JMJD6. These results suggest that JMJD6 functions directly or indirectly as an arginine demethylase of G3BP1 that promotes SG formation.