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.
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http://dx.doi.org/10.1074/jbc.M115.659433 | DOI Listing |
J Strength Cond Res
December 2024
Jayhawk Athletic Performance Laboratory, Wu Tsai Human Performance Alliance, University of Kansas, Lawrence, Kansas.
Eserhaut, DA, DeLeo, JM, and Fry, AC. Blood flow restricted resistance exercise in well-trained men: Salivary biomarker responses and oxygen saturation kinetics. J Strength Cond Res 38(12): e716-e726, 2024-Resistance exercise with continuous lower-limb blood flow restriction (BFR) may provide supplementary benefit to highly resistance-trained men.
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J Med Chem
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Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, School of Pharmaceutical Sciences, Central University of Punjab, Bathinda 151 401, India.
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Science Signaling, AAAS, Washington, DC 20005, USA.
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View Article and Find Full Text PDFSci Signal
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Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
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