Readers of histone methylarginine marks

Abstract

Arginine methylation is a common posttranslational modification (PTM) that alters roughly 0.5% of all arginine residues in the cells. There are three types of arginine methylation: monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). These three PTMs are enriched on RNA-binding proteins and on histones, and also impact signal transduction cascades. To date, over thirty arginine methylation sites have been cataloged on the different core histones. These modifications alter protein structure, impact interactions with DNA, and also generate docking sites for effector molecules. The primary "readers" of methylarginine marks are Tudor domain-containing proteins. The complete family of thirty-six Tudor domain-containing proteins has yet to be fully characterized, but at least ten bind methyllysine motifs and eight bind methylarginine motifs. In this review, we will highlight the biological roles of the Tudor domains that interact with arginine methylated motifs, and also address other types of interactions that are regulated by these particular PTMs. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.

Keywords: Arginine methylation; CARM1; Histone code; PRMT1; Tudor domain.

Figure 1. Types and sites of arginine methylation on histones

(A) Arginine residues in the tails of histones can be monomethylarginines (MMA - ●), asymmetric dimethylarginines (ADMA - ), or symmetric dimethylarginines (SDMA - ). Methyl groups are marked in red. (B) Positioning of the unstructured histone tail relative to the structure C-terminal core region. The reported sites of histone H3, H4, H2A, and H2B arginine methylation are shown. The references that first reported these methylated sites are listed in Table 1. A number of arginine methylated sites have been identified by mass spectrometric methods, but it has yet to be established which PRMTs modify them, and these sites are thus assigned question marks.

Figure 2. Domain architecture of methylarginine-binding Tudor domain-containing proteins

Alternative names are given in brackets. The proteins are not drawn to scale. The size of the human Tudor domain-containing protein in given in amino acid number at the end of each stick diagram. The references are given to the original manuscripts that present the methylarginine-binding properties of each particular tudor domain-containing protein. ZnF MYND, MYND-type zinc-finger domain; KH, K homology domain; OB-fold, oligonucleotide/oligosaccharide-binding fold; UBA, ubiquitin-associated domain; DEXD, DEAD-like helicase domain; HELIC, helicase superfamily; SN-like, staphylococcal nuclease-like domain.