Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Epigenetics & Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cell Rep. 2024 Jul 23;43(7):114459. doi: 10.1016/j.celrep.2024.114459. Epub 2024 Jul 9.
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.
甘氨酸和精氨酸丰富（GAR）基序，常见于 RNA 结合和加工蛋白中，可由蛋白质精氨酸甲基转移酶在精氨酸残基上对称（SDMA）或非对称（ADMA）二甲基化。精氨酸甲基化蛋白基序通常由含有 Tudor 结构域的蛋白识别。在这里，我们使用 GFP-Trap 鉴定了一种非 Tudor 结构域蛋白，即鳞状细胞癌抗原被 T 细胞识别 3（SART3），作为 SDMA 标记 GAR 基序的阅读器。SART3 的结构分析和突变显示，排列在两个相邻富含芳香族的半四肽重复（HAT）结构域之间的凹槽中的芳香族残基对于 SART3 识别和结合 SDMA 标记的 GAR 基序肽以及 SART3 与含有 GAR 基序的蛋白质纤维蛋白和 coilin 之间的相互作用至关重要。此外，我们表明，这种阅读器能力的丧失会影响 RNA 剪接。总的来说，我们的发现拓宽了潜在 SDMA 阅读器的范围，包括 HAT 结构域。
