Journal of Biological Chemistry 2015-07-03

Unique Features of Human Protein Arginine Methyltransferase 9 (PRMT9) and Its Substrate RNA Splicing Factor SF3B2.

Andrea Hadjikyriacou, Yanzhong Yang, Alexsandra Espejo, Mark T Bedford, Steven G Clarke

文献索引:J. Biol. Chem. 290 , 16723-43, (2015)



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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.


结构式 名称/CAS号 全部文献
硫酸 结构式 硫酸
氯化钠 结构式 氯化钠
异硫氰酸荧光素酯 结构式 异硫氰酸荧光素酯
异硫氰酸荧光素 结构式 异硫氰酸荧光素
钾 结构式
邻苯二甲醛 结构式 邻苯二甲醛
哌嗪-1,4-二乙磺酸 结构式 哌嗪-1,4-二乙磺酸
明胶 结构式 明胶
乙二醇双(2-氨基乙基醚)四乙酸 结构式 乙二醇双(2-氨基乙基醚)四乙酸
氯化钠-35cl 结构式 氯化钠-35cl