Methylation of ribosomal protein S10 by protein-arginine methyltransferase 5 regulates ribosome biogenesis.
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.
Institute of Genetics and Developmental Biology, The Key Laboratory of Molecular and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Jinqi
J
Ren
Yaqing
Y
Wang
Yuheng
Y
Liang
Yongqing
Y
Zhang
Shilai
S
Bao
Zhiheng
Z
Xu
D019943:Amino Acid Substitution; D002384:Catalysis; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D008745:Methylation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D014176:Protein Biosynthesis / Q000502:physiology*; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C000622635:RPS10 protein, human; D012269:Ribosomal Proteins; C029537:ribosomal protein S10; D000090243:Nucleophosmin; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases