{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTDRD3 is a multifunctional “reader” protein whose Tudor domain specifically recognizes asymmetrically dimethylated arginine marks deposited on histones and the RNA polymerase II C‐terminal domain, thereby acting as a transcriptional coactivator. In the nucleus, it is recruited to transcriptional start sites and estrogen‐responsive elements, where its intact Tudor domain is essential for interpreting epigenetic methyl marks to promote active transcription."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cytoplasm, however, TDRD3 plays distinct roles in RNA metabolism. It localizes predominantly to polyribosomes and stress granules, where it interacts with arginine‐methylated proteins such as FMRP and its homologs, thereby contributing to translational regulation and stress response. By acting as a scaffold, TDRD3 recruits the DNA/RNA topoisomerase Top3β to its substrates—an interaction further strengthened by an OB-fold domain—as well as partnering with helicases like DHX9 to resolve R-loop structures that otherwise impede gene expression. Moreover, TDRD3 aids in the assembly of stress granules through its methyl-binding capability, which has downstream consequences for innate immune signaling and antiviral defense."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to these molecular functions, TDRD3 has emerged as an important factor in disease processes. Its ability to regulate key gene expression programs at both transcriptional and translational levels underpins its role in promoting cancer cell proliferation, invasion, and metastasis, as evidenced in breast cancer models. Furthermore, variations in the TDRD3 gene have been linked to differences in ovarian reserve and responsiveness to controlled ovarian stimulation, offering potential insights into personalized therapeutic strategies. These findings, along with ongoing efforts to develop small molecule inhibitors that target its methyl-binding pocket, highlight TDRD3 as a promising therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yanzhong Yang, Yue Lu, Alexsandra Espejo, et al. 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