Abstract

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 Arg158 and Arg160 residues. The methylation of RPS10 at Arg158 and Arg160 plays a role in the proper assembly of ribosomes, protein synthesis and optimal cell proliferation. The RPS10-R158/160K mutant is not efficiently assembled into ribosomes and is unstable and prone to degradation by the proteasomal pathway. In nucleoli, RPS10 interacts with Nucleophosmin (NPM)/B23 and is predominantly concentrated in the granular component (GC) region which is required for ribosome assembly. The RPS10 methylation mutant interacts weakly with NPM/B23 and fails to concentrate in the GC 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.   

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 Arg158 and Arg160 residues. The methylation of RPS10 at Arg158 and Arg160 plays a role in the proper assembly of ribosomes, protein synthesis and optimal cell proliferation. The RPS10-R158/160K mutant is not efficiently assembled into ribosomes and is unstable and prone to degradation by the proteasomal pathway. In nucleoli, RPS10 interacts with Nucleophosmin (NPM)/B23 and is predominantly concentrated in the granular component (GC) region which is required for ribosome assembly. The RPS10 methylation mutant interacts weakly with NPM/B23 and fails to concentrate in the GC 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.  

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 Arg158 and Arg160 residues. The methylation of RPS10 at Arg158 and Arg160 plays a role in the proper assembly of ribosomes, protein synthesis and optimal cell proliferation. The RPS10-R158/160K mutant is not efficiently assembled into ribosomes and is unstable and prone to degradation by the proteasomal pathway. In nucleoli, RPS10 interacts with Nucleophosmin (NPM)/B23 and is predominantly concentrated in the granular component (GC) region which is required for ribosome assembly. The RPS10 methylation mutant interacts weakly with NPM/B23 and fails to concentrate in the GC 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.   

Jinqi Ren,Yaqing Wang,Yuheng liang,Yongqing Zhang,Shilai Bao and Zhiheng Xu. Methylation of ribosomal protein s10 by protein arginine methyltransferase 5 regulates ribosome biogenesis. J.Biol.Chem. DOI:10.1074/jbc.M110.103911