Identification of a small molecule antagonist for the Tudor domain of SMN

SMN functions via recognition of arginine symmetric-dimethylated proteins by its Tudor domain, and scarcity of SMN leads to Spinal Muscular Atrophy (SMA). Here we report a potent and selective antagonist targeting the Tudor domain of SMN. This compound could inhibit the interaction between SMN and R1810me2s-POLR2A mimicking the SMN depletion results, thus this SMN antagonist could be used as an efficient tool to better understand SMN9s biological functions and molecular etiology in SMA.