Institute of Genetics and Developmental Biology, The Key Laboratory of Molecular and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
J Biol Chem. 2010 Apr 23;285(17):12695-705. doi: 10.1074/jbc.M110.103911. Epub 2010 Feb 16.
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.
核糖体组装的调节是细胞数量和器官大小控制的精细调节机制。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）是一种癌蛋白，精氨酸甲基转移酶 5（PRMT5）的新底物。我们表明 PRMT5 与 RPS10 相互作用，并催化其在 Arg（158）和 Arg（160）残基上的甲基化。RPS10 在 Arg（158）和 Arg（160）上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起作用。RPS10-R158K/R160K 突变体不能有效地组装到核糖体中，并且不稳定，容易通过蛋白酶体途径降解。在核仁中，RPS10 与核磷蛋白/B23 相互作用，并主要集中在颗粒成分区域，这是核糖体组装所必需的。RPS10 甲基化突变体与核磷蛋白/B23 的相互作用较弱，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 在肿瘤发生中的一种新机制。
