Institute of Molecular Medicine I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, D-40225 Düsseldorf, Germany.
Hochschule Fresenius gGmbH, University of Applied Sciences, Limburger Straße 2, D-65510 Idstein, Germany.
Biol Chem. 2022 Aug 31;403(10):907-915. doi: 10.1515/hsz-2022-0136. Print 2022 Sep 27.
Protein-arginine methylation is a common posttranslational modification, crucial to various cellular processes, such as protein-protein interactions or binding to nucleic acids. The central enzyme of symmetric protein arginine methylation in mammals is the protein arginine methyltransferase 5 (PRMT5). While the methylation reaction itself is well understood, recruitment and differentiation among substrates remain less clear. One mechanism to regulate the diversity of PRMT5 substrate recognition is the mutual binding to the adaptor proteins pICln or RioK1. Here, we describe the specific interaction of Nuclear Factor 90 (NF90) with the PRMT5-WD45-RioK1 complex. We show for the first time that NF90 is symmetrically dimethylated by PRMT5 within the RG-rich region in its C-terminus. Since upregulation of PRMT5 is a hallmark of many cancer cells, the characterization of its dimethylation and modulation by specific commercial inhibitors presented here may contribute to a better understanding of PRMT5 function and its role in cancer.
蛋白质精氨酸甲基化是一种常见的翻译后修饰，对各种细胞过程至关重要，如蛋白质-蛋白质相互作用或与核酸结合。哺乳动物中对称蛋白质精氨酸甲基化的核心酶是蛋白质精氨酸甲基转移酶 5（PRMT5）。虽然甲基化反应本身已经很清楚，但底物的募集和分化仍然不太清楚。调节 PRMT5 底物识别多样性的一种机制是与接头蛋白 pICln 或 RioK1 的相互结合。在这里，我们描述了核因子 90（NF90）与 PRMT5-WD45-RioK1 复合物的特异性相互作用。我们首次表明，NF90 在其 C 末端 RG 丰富区域被 PRMT5 对称二甲基化。由于 PRMT5 的上调是许多癌细胞的标志，因此这里描述的其二甲基化及其对特定商业抑制剂的调节特征可能有助于更好地理解 PRMT5 的功能及其在癌症中的作用。
