15 ,
16 ,
17 ) to molecular definition of protein arginine methyltransferases (PRMTs) (
18 ,
19 ). Early mechanistic studies demonstrated that arginine methylation regulates protein–protein interactions (
20 ) and chromatin function through histone methylation by CARM1/PRMT4, PRMT1, and PRMT5 (
21 ,
22 ,
23 ), while PRMT7 is unique in only catalyzing monomethylation (
24 ,
25 ). Tool development of specific antibodies (
26 ,
27 ) and inhibitors helped advance the field. The identification of methylarginine reader proteins, including SMN and TDRD3, and the structural definition of Tudor domain recognition established principles of methylarginine-dependent signaling (
28 ,
29 ,
30 ,
31 ,
32 ,
33 ). Translational advances include the development of selective PRMT5 inhibitors (
34 ,
35 ) and the discovery that MTAP loss leads to accumulation of methylthioadenosine (MTA), creating a synthetic lethal vulnerability to PRMT5 inhibition (
36 ,
37 ,
38 ). More recent discoveries expanded methylarginine reader biology beyond Tudor domains, including SART3 (
39 ) and established MTA-cooperative PRMT5 inhibitors that exploit tumor metabolic state for selective targeting (
40 ,
41 ). Colored boxes denote conceptual categories: enzyme discovery, biochemistry, and biology (green); methylarginine readers and mechanisms (purple); and therapeutic development (orange). B , Biochemical reactions catalyzed by PRMTs. Type I, II, and III PRMTs catalyze processive methylation of arginine residues using S-adenosylmethionine (SAM) as a methyl donor, generating monomethylarginine (MMA/Rme1), asymmetric dimethylarginine (ADMA/Rme2a), or symmetric dimethylarginine (SDMA/Rme2s), with S-adenosylhomocysteine (SAH) as a byproduct. PRMT family members are classified by product specificity: Type I catalyzing MMA and ADMA (PRMT1, 2, 3, 4, 6, and 8), Type II catalyzing MMA and SDMA (PRMT5 and 9), and Type III only catalyzing MMA (PRMT7). " width="100%" height="100%">
Journal: The Journal of Biological Chemistry
Article Title: Meeting report on FASEB protein arginine methylation: mechanism to therapeutics
doi: 10.1016/j.jbc.2026.111448
Figure Lengend Snippet: Protein arginine methylation from biochemical discovery to therapeutic targeting. A , Timeline of key advances in arginine methylation biology, highlighting the progression from early biochemical identification of methylarginine and methyltransferase activity ( 15 , 16 , 17 ) to molecular definition of protein arginine methyltransferases (PRMTs) ( 18 , 19 ). Early mechanistic studies demonstrated that arginine methylation regulates protein–protein interactions ( 20 ) and chromatin function through histone methylation by CARM1/PRMT4, PRMT1, and PRMT5 ( 21 , 22 , 23 ), while PRMT7 is unique in only catalyzing monomethylation ( 24 , 25 ). Tool development of specific antibodies ( 26 , 27 ) and inhibitors helped advance the field. The identification of methylarginine reader proteins, including SMN and TDRD3, and the structural definition of Tudor domain recognition established principles of methylarginine-dependent signaling ( 28 , 29 , 30 , 31 , 32 , 33 ). Translational advances include the development of selective PRMT5 inhibitors ( 34 , 35 ) and the discovery that MTAP loss leads to accumulation of methylthioadenosine (MTA), creating a synthetic lethal vulnerability to PRMT5 inhibition ( 36 , 37 , 38 ). More recent discoveries expanded methylarginine reader biology beyond Tudor domains, including SART3 ( 39 ) and established MTA-cooperative PRMT5 inhibitors that exploit tumor metabolic state for selective targeting ( 40 , 41 ). Colored boxes denote conceptual categories: enzyme discovery, biochemistry, and biology (green); methylarginine readers and mechanisms (purple); and therapeutic development (orange). B , Biochemical reactions catalyzed by PRMTs. Type I, II, and III PRMTs catalyze processive methylation of arginine residues using S-adenosylmethionine (SAM) as a methyl donor, generating monomethylarginine (MMA/Rme1), asymmetric dimethylarginine (ADMA/Rme2a), or symmetric dimethylarginine (SDMA/Rme2s), with S-adenosylhomocysteine (SAH) as a byproduct. PRMT family members are classified by product specificity: Type I catalyzing MMA and ADMA (PRMT1, 2, 3, 4, 6, and 8), Type II catalyzing MMA and SDMA (PRMT5 and 9), and Type III only catalyzing MMA (PRMT7).
Article Snippet: In addition, Misuzu Hashimoto linked PRMT1 to CNS development and presented a model in which PRMT1 coordinates cell-type specific pathways critical for brain maturation.
Techniques: Methylation, Activity Assay, Protein-Protein interactions, Inhibition