SART3 Reads Methylarginine-Marked Glycine- and Arginine-Rich Motifs

Authors

Yalong Wang
Jujun Zhou
Wei He
Rongjie Fu
Leilei Shi
Ngoc Khoi Dang
Bin Liu
Han Xu
Xiaodong Cheng
Mark T Bedford

Publication Date

7-23-2024

Journal

Cell Reports

Abstract

Glycine- and arginine-rich (GAR) motifs, commonly found in RNA-binding and -processing proteins, can be symmetrically (SDMA) or asymmetrically (ADMA) dimethylated at the arginine residue by protein arginine methyltransferases. Arginine-methylated protein motifs are usually read by Tudor domain-containing proteins. Here, using a GFP-Trap, we identify a non-Tudor domain protein, squamous cell carcinoma antigen recognized by T cells 3 (SART3), as a reader for SDMA-marked GAR motifs. Structural analysis and mutagenesis of SART3 show that aromatic residues lining a groove between two adjacent aromatic-rich half-a-tetratricopeptide (HAT) repeat domains are essential for SART3 to recognize and bind to SDMA-marked GAR motif peptides, as well as for the interaction between SART3 and the GAR-motif-containing proteins fibrillarin and coilin. Further, we show that the loss of this reader ability affects RNA splicing. Overall, our findings broaden the range of potential SDMA readers to include HAT domains.

Keywords

Arginine, Humans, Glycine, Amino Acid Motifs, RNA-Binding Proteins, Protein Binding, RNA Splicing, HEK293 Cells, Methylation, Chromosomal Proteins, Non-Histone, Protein-Arginine N-Methyltransferases

DOI

10.1016/j.celrep.2024.114459

PMID

38985674

PMCID

PMC11370311

PubMedCentral® Posted Date

9-3-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes