Methylation of Ribosomal Protein S10 by Protein-arginine Methyltransferase 5 Regulates Ribosome Biogenesis
Methylation of Ribosomal Protein S10 by Protein-arginine Methyltransferase 5 Regulates Ribosome Biogenesis
复制标题
蛋白质精氨酸甲基转移酶 5 对核糖体蛋白 S10 的甲基化调节核糖体生物合成
DOI：
10.1074/jbc.m110.103911
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发表时间：
2010-04-23
影响因子：
4.8
通讯作者：
Xu, Zhiheng
中科院分区：
文献类型：
--
作者：
Ren, Jinqi;Wang, Yaqing;Xu, Zhiheng
核糖体组装的调节是细胞数量和器官大小控制的微调机制。许多核糖体蛋白经历翻译后修饰，但它们的确切作用仍然难以捉摸。在这里，我们报告核糖体蛋白 s10 (RPS10) 是癌蛋白蛋白精氨酸甲基转移酶 5 (PRMT5) 的新型底物。我们发现 PRMT5 与 RPS10 相互作用并催化其在 Arg(158) 和 Arg(160) 残基处的甲基化。 RPS10 在 Arg(158) 和 Arg(160) 处的甲基化在核糖体的正确组装、蛋白质合成和最佳细胞增殖中发挥着重要作用。 RPS10-R158K/R160K 突变体不能有效地组装成核糖体，并且不稳定并且容易被蛋白酶体途径降解。在核仁中，RPS10 与核磷蛋白/B23 相互作用，并且主要集中在核糖体组装所需的颗粒成分区域。 RPS10 甲基化突变体与核磷蛋白/B23 相互作用较弱，无法集中在颗粒成分区域。我们的结果表明PRMT5可能通过核糖体蛋白的甲基化来调节细胞增殖，从而揭示了PRMT5在肿瘤发生中的新机制。
Modulation of ribosomal assembly is a fine tuning mechanism for cell number and organ size control. Many ribosomal proteins undergo post-translational modification, but their exact roles remain elusive. Here, we report that ribosomal protein s10 (RPS10) is a novel substrate of an oncoprotein, protein-arginine methyltransferase 5 (PRMT5). We show that PRMT5 interacts with RPS10 and catalyzes its methylation at the Arg(158) and Arg(160) residues. The methylation of RPS10 at Arg(158) and Arg(160) plays a role in the proper assembly of ribosomes, protein synthesis, and optimal cell proliferation. The RPS10-R158K/R160K mutant is not efficiently assembled into ribosomes and is unstable and prone to degradation by the proteasomal pathway. In nucleoli, RPS10 interacts with nucleophosmin/B23 and is predominantly concentrated in the granular component region, which is required for ribosome assembly. The RPS10 methylation mutant interacts weakly with nucleophosmin/B23 and fails to concentrate in the granular component region. Our results suggest that PRMT5 is likely to regulate cell proliferation through the methylation of ribosome proteins, and thus reveal a novel mechanism for PRMT5 in tumorigenesis.