Zhu Fen, Rui Lixin
Department of Medicine and Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.
Genes Dis. 2019 Jun 19;6(3):247-257. doi: 10.1016/j.gendis.2019.06.002. eCollection 2019 Sep.
Arginine methylation is a common posttranslational modification that governs important cellular processes and impacts development, cell growth, proliferation, and differentiation. Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs), which are classified as type I and type II enzymes responsible for the formation of asymmetric and symmetric dimethylarginine, respectively. PRMT5 is the main type II enzyme that catalyzes symmetric dimethylarginine of histone proteins to induce gene silencing by generating repressive histone marks, including H2AR3me2s, H3R8me2s, and H4R3me2s. PRMT5 can also methylate nonhistone proteins such as the transcription factors p53, E2F1 and p65. Modifications of these proteins by PRMT5 are involved in diverse cellular processes, including transcription, translation, DNA repair, RNA processing, and metabolism. A growing literature demonstrates that PRMT5 expression is upregulated in hematologic malignancies, including leukemia and lymphoma, where PRMT5 regulates gene expression to promote cancer cell proliferation. Targeting PRMT5 by specific inhibitors has emerged as a potential therapeutic strategy to treat these diseases.
精氨酸甲基化是一种常见的翻译后修饰，它调控重要的细胞过程，并影响发育、细胞生长、增殖和分化。精氨酸甲基化由蛋白质精氨酸甲基转移酶（PRMTs）催化，这些酶分为I型和II型，分别负责不对称和对称二甲基精氨酸的形成。PRMT5是主要的II型酶，它催化组蛋白的对称二甲基精氨酸，通过产生包括H2AR3me2s、H3R8me2s和H4R3me2s在内的抑制性组蛋白标记来诱导基因沉默。PRMT5还可以使非组蛋白如转录因子p53、E2F1和p65发生甲基化。PRMT5对这些蛋白质的修饰参与多种细胞过程，包括转录、翻译、DNA修复、RNA加工和代谢。越来越多的文献表明，PRMT5在血液系统恶性肿瘤（包括白血病和淋巴瘤）中表达上调，在这些肿瘤中PRMT5调节基因表达以促进癌细胞增殖。通过特异性抑制剂靶向PRMT5已成为治疗这些疾病的一种潜在治疗策略。
