Glycineargininerich

Glycine-arginine-rich (GAR) domains are low-complexity regions found in a subset of RNA-binding proteins, characterized by a high frequency of glycine and arginine residues, often arranged as RG or RGG repeats. These regions are typically intrinsically disordered and can be located at the N- or C-terminus of proteins such as fibrillarin and nucleolin, as well as various heterogeneous nuclear ribonucleoproteins (hnRNPs).

GAR domains play roles in RNA binding and in mediating protein–RNA and protein–protein interactions that contribute to RNA processing, ribosome biogenesis, and the organization of nuclear compartments. They are also implicated in subcellular localization, notably targeting proteins to the nucleolus or to other nuclear bodies, and can participate in phase separation processes that form ribonucleoprotein assemblies.

Post-translational modification of arginine residues within GAR motifs is common, particularly through arginine methylation by protein arginine methyltransferases (PRMTs). This methylation can alter RNA-binding affinity, modulate protein–protein interactions, influence subcellular localization, and affect the dynamics of condensates formed by GAR-containing proteins.

Biological significance and disease relevance: GAR-containing proteins participate in transcriptional regulation, RNA maturation, and ribosome biogenesis. Dysregulation of GAR domain function or arginine methylation has been associated with various diseases, including cancer and neurodegenerative conditions, making the study of GAR domains an active area of research.

Examples of GAR-domain proteins include fibrillarin and nucleolin, with other RG-rich proteins contributing to diverse aspects of RNA metabolism and nuclear architecture.