SART3 is a Novel Rme2s Reader
Arginine methylation is a ubiquitous post-translational modification involved in many biological processes such as transcription, cell signaling and RNA splicing. Tudor domains by far are the major effector domain family for arginine methylation mark recognition. Here we characterize SART3 as a novel selective reader for symmetric dimethylarginine (Rme2s) marks. SART3 harbors a series of HAT (Half-a-TPR) repeats that are aromatic-rich, and it is this region that binds Rme2s motifs. An analysis of the reported structure of the HAT repeats of SART3 identified a putative aromatic cage that potentially “read” the Rme2s-modified motifs, and the key aromatic residues required for Rme2s recognition were identified. We further confirm that this Rme2s reader ability is important for SART3-mediated RNA splicing. Together, our studies revealed that the evolutionarily conserved SART3 HAT domain was a novel reader of Rme2s mark involved in RNA splicing. Overall design: Hela SART3-KO was restored with SART3 wild-type(WT) or mutants(Y112A, W377A), total RNA was harvested for RNA-seq analysis