Protein l-Arginine Methylation of RNA-Binding Proteins and Their Impact on Human Diseases

RNA-binding proteins (RBPs) are important for regulating the transcriptional expression of genes, as well as controlling the production of multiple transcriptional isoforms from a single gene by modulating pre-mRNA splicing [Lunde et al. (Nat Rev Mol Cell Biol 8:479–490, 2007)]. These proteins influence multiple aspects of RNA metabolism, including maturation, surveillance, subcellular localization, nucleocytoplasmic transport, and degradation [Lunde et al. (Nat Rev Mol Cell Biol 8:479–490, 2007)]. RNA-binding proteins contain one or more RNA-binding domains (RBDs) that specify their association with RNAs. Examples of common RBDs include the RNA recognition motif (RRM), K-homology (KH) domain, RGG box/domain, Sm domain, zinc finger, and Piwi/Argonaute/Zwille domain [Lunde et al. (Nat Rev Mol Cell Biol 8:479–490, 2007)]. These RBDs act as modules that can be combined and arranged to expand the functional ability of an RBP. This modular architecture provides versatility: RBP binding with high affinity and specificity to a specific target can be achieved by combining different RBDs that individually recognize shorter RNA sequences with weak affinity. Many RBPs contain additional post-translational modifications that can influence their biochemical properties. One such modification that has been found in many RBPs is protein arginine methylation [Bedford and Clarke (Mol Cell 33:1–13, 2009)]. Recent findings have implicated this modification as a major regulator of RBP function within a cell [Bedford and Clarke (Mol Cell 33:1–13, 2009)], thereby pointing to the potential of this modification serving an important role in the cause or progression of human diseases.