title: Peptides with sequences similar to glycine, arginine-rich motifs in proteins interacting with RNA are efficiently recognized by methyltransferase(s) modifying arginine in numerous proteins.
abstract: Several proteins that interact with RNA, e.g. the heterogenous ribonucleoprotein particle A and B proteins, fibrillarin and nucleolin, contain the modified amino acid NG,NG-dimethylarginine. Here, we report that two synthetic peptides, Ac-GGRGGFGGRGGFGGRGGFG-NH2 (R3) and GGFGGRGGFG-NH2 (R1), which are based on methylated sequences in fibrillarin and nucleolin, inhibit the methylation of a large majority of the methyl-accepting proteins observed in extracts of adenosine dialdehyde-treated PC12 cells. Concomitantly, the peptides themselves become methylated, suggesting that they compete for the same enzyme that carries out the bulk of N-methylation in PC12 cells. R3 potently inhibits formation of NG,NG-dimethylarginine in PC12 substrates, with a lesser effect on NG-monomethylarginine and NG,N'G-dimethylarginine. Bovine brain contains an activity that methylates PC12 methyl acceptors. After partial purification, the bovine methyltransferase efficiently modifies R3 and R1, yielding half-maximal rates of methylation at approximately 0.2 and approximately 2 microM peptide, respectively. A search of the GenPept database for the FGGRGGF motif revealed 13 candidate methyl acceptors containing arginine and at most two similar substitutions or one mismatch. Of these, 10 are known or presumed to interact with RNA. These findings are consistent with the hypothesis that a majority of proteins containing NG,NG-dimethylarginine interact with RNA.
authors.affiliation: School of Biological Sciences, University of California, Irvine 92717-4550.
authors.forename: J
authors.initials: J
authors.lastname: Najbauer
authors.forename: B A
authors.initials: BA
authors.lastname: Johnson
authors.forename: A L
authors.initials: AL
authors.lastname: Young
authors.forename: D W
authors.initials: DW
authors.lastname: Aswad
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005998:Glycine; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D000097796:Nucleolin
chemical_list: D001120:Arginine; D002868:Chromosomal Proteins, Non-Histone; D005998:Glycine; D047908:Intracellular Signaling Peptides and Proteins; D008780:Methyltransferases; D009687:Nuclear Proteins; D010455:Peptides; D010750:Phosphoproteins; D011484:Protein-Arginine N-Methyltransferases; D012313:RNA; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000097796:Nucleolin; C047458:fibrillarin; C018524:N,N-dimethylarginine; C077013:PRMT2 protein, human