Effectors and effects of arginine methylation

Abstract

Arginine methylation is a ubiquitous and relatively stable post-translational modification (PTM) that occurs in three types: monomethylarginine (MMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Methylarginine marks are catalyzed by members of the protein arginine methyltransferases (PRMTs) family of enzymes. Substrates for arginine methylation are found in most cellular compartments, with RNA-binding proteins forming the majority of PRMT targets. Arginine methylation often occurs in intrinsically disordered regions of proteins, which impacts biological processes like protein-protein interactions and phase separation, to modulate gene transcription, mRNA splicing and signal transduction. With regards to protein-protein interactions, the major 'readers' of methylarginine marks are Tudor domain-containing proteins, although additional domain types and unique protein folds have also recently been identified as methylarginine readers. Here, we will assess the current 'state-of-the-art' in the arginine methylation reader field. We will focus on the biological functions of the Tudor domain-containing methylarginine readers and address other domains and complexes that sense methylarginine marks.

Keywords: PRMTs; R-loops; Tudor domains; phase separation.

Figure 1.. A Summary of the known and likely methylarginine effector proteins.

(A) The central circle shows the structure of the SDMA and ADMA marks, which can be recognized by the listed protein and protein complexes. Concentric to that lie the known and well-characterized readers of methylarginine marks. Tudor domain-containing proteins that are SDMA effectors (green tones). ADMA effectors include a single Tudor domain protein, three proteins with unique folds (blue tones), and two protein complexes (purple tones). (B) A second group of likely SDMA effector are restricted to male germ cells and are all Tudor domain-containing proteins (orange tones).