{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRPF19 is a highly conserved, multifunctional protein that plays a critical role in pre-mRNA splicing. It is a central component of the spliceosome’s activation machinery, assembling into multimeric complexes with partners such as CDC5L, PRL1, SPF27, and CTNNBL1, and collaborates with splicing factors like U2AF65 and Blom7α to ensure efficient splicing and alternative exon selection. Structural studies have revealed that its WD40 repeat domain is uniquely organized to facilitate interactions necessary for spliceosome assembly, while biochemical complementation and immunodepletion experiments confirm its indispensable role in catalysis during early and late pre-mRNA processing steps."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in splicing, PRPF19 operates as an E3 ubiquitin ligase that is acutely involved in safeguarding genome integrity. It is recruited to sites of DNA damage by binding to RPA-coated single-stranded DNA, thereby promoting RPA ubiquitylation and facilitating the proper accumulation of ATRIP for ATR kinase activation. PRPF19 and its associated complexes also contribute to the repair of DNA interstrand cross-links, double-strand breaks, and stalled replication forks. The protein’s modification via autoubiquitylation and ATM‐dependent phosphorylation further underpins its functions in S phase progression, homologous recombination, and even the modulation of cellular senescence through regulation of alternative splicing of key cell cycle regulators."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in splicing and DNA repair, PRPF19 has emerged as a key modulator in oncogenesis and cellular homeostasis. 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