{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSF3B2, also known as SAP145, is a core component of the U2 small nuclear ribonucleoprotein complex that plays a pivotal role in pre‐mRNA splicing and the regulation of alternative splicing. Its activity is fine‐tuned by post‐translational modifications; for example, PRMT9‐mediated symmetric dimethylation of specific arginine residues on SF3B2 is critical for substrate recognition and splicing regulation. In addition, structural studies have revealed that SF3B2 engages in highly conserved helix–helix interactions with other spliceosomal subunits—such as SF3B49—to ensure proper assembly and functionality of the splicing machinery. Dynamic regulation of SF3B2 expression during cellular transitions, including T lymphocyte activation, further underscores its central role in coordinating RNA processing with broader cellular programs."}, {"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": "\nBeyond its canonical function in RNA splicing, SF3B2 contributes to the regulation of cell cycle progression and genomic stability. The HIV-1 accessory protein Vpr exploits SF3B2 by binding to its CUS1 domain, thereby disassembling the SF3B2–SAP49 complex and triggering ATR-dependent checkpoint activation that results in G2 cell cycle arrest. In parallel, as part of the larger SF3B complex, SF3B2 modulates DNA double-strand break repair by affecting the mRNA levels of repair factors and promoting the recruitment of CtIP to sites of damage—a process crucial for homologous recombination and genome integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in SF3B2 expression or function are associated with diverse human diseases. In hepatocellular carcinoma, up-regulation of SF3B2—as part of a broader enhancement of spliceosome pathway genes—has been observed, suggesting that aberrant splicing contributes to tumorigenesis. In prostate cancer, increased SF3B2 expression drives the generation of oncogenic androgen receptor splice variants (notably AR-V7), which in turn promote aggressive cancer phenotypes and resistance to AR-targeted therapies. Moreover, binding of G-quadruplex-forming oligonucleotides to SF3B2 has been shown to suppress interferon-stimulated gene induction in cancer cells, highlighting an additional role in modulating stress and immune response pathways. Finally, loss-of-function (haploinsufficient) variants in SF3B2 have emerged as a major genetic cause of craniofacial microsomia, linking defective splicing to developmental anomalies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephen J Orr, Daniel R Boutz, Rong Wang, et al. 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