Unique Features of Human Protein Arginine Methyltransferase 9 (PRMT9) and Its Substrate RNA Splicing Factor SF3B2
| Autor: | Yanzhong Yang, Mark T. Bedford, Alexsandra Espejo, Steven Clarke, Andrea Hadjikyriacou |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Protein-Arginine N-Methyltransferases
RNA splicing Arginine PRMT Amino Acid Motifs protein methyltransferase Crystallography X-Ray Medical and Health Sciences Biochemistry Substrate Specificity Conserved sequence Mice enzyme mutation Protein methylation Crystallography symmetric dimethylarginine Protein arginine methyltransferase 5 protein arginine N-methyltransferase 5 RNA-Binding Proteins Methylation Biological Sciences protein arginine methylation RNA Splicing Factors PRMT9 Biochemistry & Molecular Biology RNA Splicing 1.1 Normal biological development and functioning Molecular Sequence Data Biology Splicing factor Underpinning research Genetics Animals Humans Protein Methyltransferases Amino Acid Sequence protein methylation Molecular Biology S-adenosylmethionine F-Box Proteins Alternative splicing Cell Biology Chemical Sciences Enzymology X-Ray Biocatalysis Generic health relevance |
| Zdroj: | The Journal of biological chemistry, vol 290, iss 27 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.659433 |
| Popis: | Human protein arginine methyltransferase (PRMT) 9 symmetrically dimethylates arginine residues on splicing factor SF3B2 (SAP145) and has been functionally linked to the regulation of alternative splicing of pre-mRNA. Site-directed mutagenesis studies on this enzyme and its substrate had revealed essential unique residues in the double E loop and the importance of the C-terminal duplicated methyltransferase domain. In contrast to what had been observed with other PRMTs and their physiological substrates, a peptide containing the methylatable Arg-508 of SF3B2 was not recognized by PRMT9 in vitro. Although amino acid substitutions of residues surrounding Arg-508 had no great effect on PRMT9 recognition of SF3B2, moving the arginine residue within this sequence abolished methylation. PRMT9 and PRMT5 are the only known mammalian enzymes capable of forming symmetric dimethylarginine (SDMA) residues as type II PRMTs. We demonstrate here that the specificity of these enzymes for their substrates is distinct and not redundant. The loss of PRMT5 activity in mouse embryo fibroblasts results in almost complete loss of SDMA, suggesting that PRMT5 is the primary SDMA-forming enzyme in these cells. PRMT9, with its duplicated methyltransferase domain and conserved sequence in the double E loop, appears to have a unique structure and specificity among PRMTs for methylating SF3B2 and potentially other polypeptides. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|