SMN, the product of the spinal muscular atrophy gene, binds preferentiallyto dimethylarginine-containing protein targets

The survival of motor neurons protein (SMN), the product of the neurodegene rative disease spinal muscular atrophy (SMA) gene, functions as an assembly factor for snRNPs and likely other RNPs. SMN binds the arginine- and glyci ne-rich (RG) domains of the snRNP proteins SmD1 and SmD3. Specific arginine s in these domains are modified to dimethylarginines, a common modification of unknown function. We show that SMN binds preferentially to the dimethyl arginine-modified RG domains of SmD1 and SmD3. The binding of other SMN-int eracting proteins is also strongly enhanced by methylation. Thus, methylati on of arginines is a novel mechanism to promote specific protein-protein in teractions and appears to be key to generating high-affinity SMN substrates . It is reasonable to expect that protein hypomethylation may contribute to the severity of SMA.